VYGR - NASDAQ

Good afternoon, and welcome to the Voyager Therapeutics Second Quarter 2024 Financial Results Conference Call. At this time all participants are in a listen-only mode. There will be a question-and-answer session at the end of this call. Please note that today's call is being recorded. A replay of today's call will be available on the Investors section of the company website approximately two hours after completion of this call. I would now like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer at Voyager.

Thank you, and good afternoon. We issued our second quarter 2024 financial results press release this afternoon. The press release and 10-Q are available on our website. Joining me on today's call are Dr. Al Sandrock, our Chief Executive Officer; Dr. Toby Ferguson, our Chief Medical Officer; and Dr. Nathan Jorgensen, our Chief Financial Officer. We will also be joined for the Q&A portion of the call by Dr. Todd Carter, our Chief Scientific Officer. Before we get started, I'd like to remind everyone that during this call, Voyager representatives may make forward-looking statements as noted in Slide 2 of today's deck. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings, which are available on our website for additional detail. And now, I will turn the call over to Al.

Good afternoon, everyone, and thank you for joining us. Please turn to Slide 3. At Voyager, we are leveraging the power of human genetics to discover and develop transformative medicines that address the root cause of neurological diseases. We have made tremendous progress toward this goal in 2024, including the achievement of several important milestones in the second quarter. In May, we dosed the first healthy volunteers in the Phase Ia single ascending dose trial of VY7523, formerly called VY-TAU01, our anti-tau antibody designed to inhibit the spread of pathological tau in Alzheimer's disease. Enrollment in this study is on track and we expect to report topline safety and pharmacokinetic data in the first half of next year. Toby will provide additional detail on our tau-directed programs in just a bit. We continue to advance our robust pipeline of wholly-owned and partnered CNS gene therapy programs and we continue to expect IND filings for three of these programs next year. In the second quarter, we completed a pre-IND meeting with FDA and initiated GLP toxicology studies for VY9323, our wholly-owned SOD1 silencing gene therapy program for SOD1 ALS. Also this quarter, we selected a development candidate in our GBA1 gene therapy program partnered with Neurocrine, triggering a $3 million milestone payment to Voyager. This follows the development candidate selection that occurred in the first quarter on our Neurocrine partner gene therapy program for Friedreich's ataxia. In June, we appointed Nathan Jorgensen as Chief Financial Officer of Voyager. Nate brings a highly differentiated breadth of experience spanning investment banking, health care investing, operational leadership roles in biotech and a PhD in neuroscience. I'm already seeing the benefits of his strategic financial expertise. Our team presented an impressive body of data at ASGCT 2024 in May, including data on our second-generation TRACER capsids, their translatability as evidenced by cross species and receptor data and activity against therapeutic targets in Alzheimer's disease and ALS. These posters and presentations are available on our website in case you missed them. Finally, we ended the second quarter with a strong cash position of approximately $371 million, which based on our current operating plans, we expect to provide runway through multiple clinical data readouts into 2027. The progress we made in the second quarter feeds into our four pillars of value, which are outlined on Slide 4. First is our pipeline of 4 wholly-owned and 13 partnered programs. As I mentioned, our anti-tau antibody, VY7523 is in a single ascending dose trial and we have three gene therapies tracking to INDs next year. This sets up for multiple potential data readouts in 2025 and 2026. Second is our industry-leading TRACER platform for the discovery of novel AAV capsids to enable CNS gene therapy. As the data we presented ASGCT reinforced, our second-generation capsids have demonstrated robust transduction of key CNS cell types and significant liver detargeting following a single IV dose. These capsids have enabled the selection of multiple development candidates in our wholly-owned and partnered gene therapy programs. Third, we have blue-chip partnerships with some of the world's experts in neurology and gene therapy, including Neurocrine, Novartis and Alexion. In total, our partnered programs could generate up to $8.2 billion in longer-term milestone payments. Finally, we continue to explore the potential to leverage receptors we have identified to shuttle non-viral genetic medicines into the brain. Ultimately, we aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, broadening our impact. With that, I'll turn the call over to Toby to share his conviction on our tau and gene therapy programs.

Thanks, Al, and good afternoon. Please turn to Slide 5. This slide summarizes the four wholly-owned programs and 13 partner programs that Al mentioned earlier. We won't discuss all of these programs today, but I do want to spend a few minutes on some of our more advanced programs. Turning to Slide 6. I want to focus for a moment on our two wholly-owned programs that target tau. There are a few reasons we believe that tau is critically important for the treatment of Alzheimer's disease. First, the presence of tau pathology in the brain is a defining feature of the disease. Second, a wealth of evidence demonstrates that the accumulation and spread of tau pathology to the blade closely correlates with clinical decline in Alzheimer's disease. And third, the spread of tau pathology can be readily visualized in vivo with tau PET imaging, enabling the enrollment of appropriate individuals in clinical studies and provided a quantitative biological readout that is likely to predict clinical outcomes. Importantly, recent third-party clinical data generated using an intrathecally administered tau-directed antisense oligonucleotide showed that reducing tau expression was associated with a favorable trends on clinical outcomes. At Voyager, we are advancing two complementary approaches to reduce tau pathology in Alzheimer's disease. VY7523, formerly called VY-TAU01 is an anti-tau antibody designed to inhibit the cell-to-cell spread of pathological tau in the brain. In contrast to third-party anti-tau antibody approaches had targeted the N-terminal of tau and have been unsuccessful in the clinic. VY7523 targets a C-terminal epitope of pathological tau. In an in vivo model of human tau spread, the [indiscernible] surrogate of VY7523, inhibit tau spread by approximately 70%, while N-terminal directed antibodies that were ineffective in the clinic were also ineffective in the model. This quarter, we dosed the first participant in the Phase Ia single ascending dose trial of VY7523 in healthy volunteers. This randomized double-blind placebo-controlled trial is designed to evaluate the safety and pharmacokinetics of VY7523 at approximately 48 participants across multiple cohorts. Enrollment in this trial is on track and we expect to report topline data in the first half of next year. We then plan to conduct a multiple ascending dose study in participants with early Alzheimer's disease. We expect to initiate this trial next year and generate initial tau imaging data in the second half of 2026. That has the potential to show slowing of tau spread. Complementing this antibody-based approach, we are also advancing a Tau Silencing Gene Therapy program. This program deploys a tau-targeted siRNA packaged in an IV-administered TRACER capsid. Using this approach, we've demonstrated robust reductions in human tau mRNA and protein across the brain following a single IV administration in mice expressing human tau. We believe this program has the potential to provide a transformative single-dose treatment for Alzheimer's disease and we anticipate filing an IND in 2026. Turning to Slide 7. In addition to our programs targeting tau, we're also advancing three gene therapy programs for which we expect IND filings next year. They include VY9323, a wholly-owned SOD1 silencing program, targeting the genetic cause of SOD1-ALS. The Neurocrine partnered Friedreich's ataxia placement program targeting the genetic cause of Friedreich's ataxia and the Neurocrine partnered GBA gene replacement program for Parkinson's disease and other GBA1-mediated diseases. As a reminder, we have demonstrated that a single IV administration of VY9323 at a clinically relevant dose of 3E13 vector genomes per kilogram reduced SOD1 mRNA up to 80% in the spinal cord motor neurons in non-human primates. We expect to file an IND for VY9323 in the middle of next year and initiate clinical trial in SOD1-ALS patients after the IND is accepted. Consistent with our strategy to generate rapid proof of biology in our clinical programs, we aim to assess validated biomarkers of target engagement and disease progression in this trial, including measured levels of SOD1 in the cerebral spinal fluid and levels of neurofilament in the plasma. Importantly, since this program has the potential to generate the first clinical data for gene therapy employing a TRACER capsid, we believe it could further derisk our broader CNS gene therapy pipeline. With that, I'll turn the call over to Nate.

Thanks, Toby. I just want to say that I'm grateful to be here today and to be a member of the Voyager team. Given my background in neuroscience and my experience on the buy-side, the sell-side and as a public company CFO, I am deeply familiar with the tremendous value remaining to be unlocked in treating CNS diseases as well as the risk. One of the reasons that I joined Voyager was that I appreciated the way the company is working to systematically reduce risk across this pipeline and thereby increase the probability that its potentially transformative programs will succeed in the clinic. On Slide 8, I have outlined what I see as four compelling elements of this derisking strategy. Number one, reducing risk at the target level by focusing on targets validated by human genetics. Number 2, reducing risk at the delivery level by pioneering an industry-leading platform aimed to overcome delivery hurdles posed by the blood brain barrier. And three, reducing risk at the clinical development level by focusing on disease areas and biomarkers that enable an efficient path to clinical proof of biology and value creation. And one, dear to my heart, reducing risk at the financial level by selectively partnering programs to share risk, create near-term value and reduce internal R&D spend while maintaining substantial upside. Given the high unmet need in the neuro space and Voyager's unparalleled team of experts in neuroscience drug development, I believe Voyager is uniquely positioned to overcome fundamental challenges in neurology and create tremendous value for both patients and shareholders. I look forward to connecting with many of you at upcoming investor conferences and events and please do not hesitate to reach out with any questions. With that, I'll pass it back over to Al.

Thanks, Nate. As you can see on Slide 9, Voyager continues to deliver on expectations for 2024. We have advanced our pipeline, our platform and our partnerships as well as executed a $100 million public offering and strengthened our leadership team. With a robust slate of clinical milestones expected in the next 12 to 24 months, a maturing partnership portfolio with top-tier collaborators and cash runway into 2027, we believe Voyager is poised to drive significant value creation over both the near and long-term. Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients. With that, we will open the call for questions. Operator?

Thank you. At this time we will conduct a question-and-answer session. [Operator Instructions] First question comes from Jack Allen with Baird. Go ahead, your line is open.

Great. Thank you so much for taking the question and all updates. Congratulations on the progress made over the course of the quarter. I apologize, I was coming in and out of as I head to [Ashtabula]. I actually lost power where I am here in Ohio. But I wanted to ask about the cadence of the three gene therapy programs that are expected to enter the clinic in 2025. Do you have a sense for which of those programs may be more advanced as compared to others? And then as it relates to the internal SOD1-ALS program, how quickly can we look at impact on biomarkers there? I think it was a matter of weeks or months as it relates to the ASO's impact. I'd love to hear your thoughts as it relates to how quickly we could see early indications of effect from that gene therapy that's internally owned?

Thanks, Jack. This is Al. I'll start and then I'll ask Toby to answer the second question. So in terms of the cadence, I mean, the one thing that we are in control of is our wholly-owned SOD1 gene therapy program and we expect to file an IND roughly in mid-2025 timeframe. And hopefully, we'll get sales through the FDA process and we can start shortly thereafter in clinical trials. In terms of the other programs, those are partnered programs. We know from our partners that they expect to file IND in 2025 as well. But other than that, I'm not certain I can say more about the cadence. Toby?

Jack, thanks for the question. I think you've got the idea correct. I think fundamentally, the tofersen program has taught us that you can see – you can observe with effective SOD reduction, a change in neurofilament and also you can measure target engagement by measuring CSF SOD1 to remind that the Biogen program saw about a 40% reduction of CSF SOD1 and that's the first biomarker we would be looking at. And of course, we'll also be looking at neurofilament to understand the changes observed there.

Great. Thank you so much for that response. Maybe just Toby, really briefly, how quickly was that effect on SOD1 in neurofilament light chain seen in the Biogen setting? I'm trying to get a sense for how quickly we could see early indications of efficacy?

So fundamentally, remember, Biogen is intrathecally administered ASO. Those neurofilament changes started to be observed by eight weeks. By 12 to 16 weeks, they'd reach their neither. I think the point to make here is though this is an ASO. We, of course, are administering gene therapy and so those timelines may be different and we need to work through that.

And what about the SOD1?

And SOD1, I think that can be seen as early as starting to be seen in four weeks, but really 12 weeks is really when you start to see the effect for SOD1.

Great. Thank you so much. Thank you guys. Congratulations on the progress. I'll jump back in the queue.

[Operator Instructions] The next question comes from Divya Rao with TD Cowen. Go ahead, your line is open.

Hi, guys. This is Divya on for Phil. I have two questions. One is for VY7523. Could you give us an idea of how many dose levels you're exploring? And then based on the preclinical models that you have so far, how many doses do you think you just cut through to hit what would be considered an active dose? And then I have a follow-up question.

Divya, thank you for the question. This is Toby. Fundamentally, to remind the single ascending doses in healthy volunteers, we're looking at multiple doses. We haven't disclosed those, but frankly, we think based on the preclinical models that measure tau spread, we think we understand the exposures we need to get tau spread. And based on the SOD data, we will understand those exposures and move forward with a MAD study next year.

Todd, do you want to answer the second part?

So, the second part of the question being, what are the doses that we expect to be able to achieve something relative to our preclinical models. What we've done is we're basing it off of the modeling for the PK studies and we know that we're able to achieve approximately 70% or better knockdown, a reduction of tau pathology in the [seating] model that Toby referred to. So, what we're doing is we're aiming to achieve the level of exposure of our antibody in the brain in the CNS patients to that level that we needed to achieve that 70% knockdown. So, our dosing is based on that correlation. Of course, the data that we get from the PK in the studies will really dictate when we achieve that.

Got it. That’s helpful. And then my second question is just there's two kind of programs that you're looking at going after tau specifically in patients with Alzheimer's. Should we think of those programs both kind of going after the same population? Or do you think that the vectorized – or sorry, the tau silencing gene therapy lends itself to a specific subpopulation? Thank you.

I think fundamentally, I'd say that, one, the tau antibody program is ahead and there remains a strong unmet need in patients with Alzheimer's disease. I think we've seen from the bit amyloid data that there continues to be disease progression. And so in first and foremost, we think tau is an incredibly important target in and of itself. And we've be incredibly excited to advance an antibody and an ASO that knocks down all tau. So, I think that's sort of the most straight forward point I would make.

Yes. Maybe I could add that in the case of the spreading, the antibody is meant to block the spread of pathological tau. So, we would want to choose patients where the spread has just started potentially and then chose an area of the brain to measure the spread to. And so in the staging, it would be Stage 2 or Stage 3 patients likely. The case of the knockdown, we're going to be able to follow – what we're going to be tracking the BIIB080 program, right? And that's a knockdown approach using an ASO. So there, we're going to learn a lot from that. And I suspect we'll model our study after that, including the stage of patients.

Thank you. [Operator Instructions] Next question comes from Ry Forseth with Guggenheim Securities. Go ahead, your line is open.

This is Ry from Debjit's team. Could you discuss the potential of the TRACER platform to yield capsids with multi-organ specificity potentially fit for addressing indications, such as DM1, where there's both central and neuromuscular pathology?

Well, that's a – I'll start and Todd can finish. Yes. In some ways, it applies not just to DM1, but also Friedreich's Ataxia, which involves the nervous system in the heart. The way we look at it is that, TRACER finds – looks for variations in the capsids that given – endows the capsid with an additional trophic activity. So, in our hands, since AAV9 works pretty well for cardiac muscle all on its own, you don't have to necessarily enhance that. And if the TRACER-derived capsid gets the additional property of also getting into the brain, but retains its property of transducing heart muscle, then that would be an ideal capsid. And I bring up the heart, by the way, because DM1 also affects the heart. In terms of skeletal muscle, there, we do look at skeletal muscle transduction, and we will choose capsids that obviously can do that. We haven't said that we have a DM1 program, by the way, but that's why I started with Friedreich's Ataxia. But, Todd, do you want to...

Sure. So we do look at quite a wide variety of tissues throughout the non-human primates when we're identifying and selecting our capsids. And in fact, for any given disease, we actually build a capsid profile, a target capsid profile. Different diseases, different CNS diseases have different relative delivery needs to even different parts of the brain. We also look for detargeting for off-target tissues like the liver. And so, we do evaluate quite a number of tissues. And what we are seeing is that, we have different kinds of capsid profiles that are coming out of our capsid screens. So what that results in are different capsid families that have different potentials and opportunities for being deployed for different diseases. And that includes greater or lesser delivery to places like the muscle, the heart, various brain regions, and of course, off-targets. So I think the answer is, we do see the opportunity for TRACER to deliver opportunities for, not just the CNS, but in other diseases as well.

Thank you.

[Operator Instructions] Next question comes from David with Citigroup. Go ahead, your line is open.

This is [Sean] on David's team from Citi. Thank you for taking our questions. I guess, one question that we have is, can you speak to the potential competitive positioning of your anti-tau therapy versus Biogen's program? And second question relates to the SOD1 silencing gene therapy. I'm just curious, what are some of the remaining gating factors to get to the IND filing? Thank you.

Well, I'll answer the first question on tau, and then maybe Toby could answer the second question on SOD1. So, in terms of Biogen, they have a BIIB080 program. They did have an anti-tau program directed against the N-terminal as Toby mentioned. That antibody was terminated after not producing the results that were acceptable. And so, there are, however, a number of other companies pursuing anti-tau antibodies, at least four other companies that we know of targeting various different epitopes. None are, again, directed against the N-terminal, probably because everybody thinks that the N-terminal is not a great epitope. But some are targeting the mid-domain, some are targeting the MTBR, and like us, one other company is targeting the C-terminal. Fundamentally, the vectorized siRNA approach is, as Toby indicated, we're not in the clinic yet. We do expect to file an IND in 2026. But – so we're way behind, if you will, the BIIB080 program, which is already in the clinic and starting to produce some interesting results. I would just add that in concept, it's very similar in the sense that it's knocking down the expression of all forms of tau, both intracellular and extracellular. So it's decreasing expression of tau, essentially in the nervous system. So in that sense, it produces, we think, a relatively equivalent effect on tau. Toby, do you want to take the second question?

Sure. Maybe I'd add one other point on that is on the tau program before I do, just to highlight that the Biogen program, of course, is intrathecally administered, and our program is a onetime IV administrative program, sort of in keeping with our strategy of pursuing with our novel TRACER capsids, relatively derisked targets. On the SOD program, I think fundamentally what we've highlighted is that, that program which we closed that program as we started the toxicology programs, and that's the main key next step for moving the program forward for the IND.

Thank you.

[Operator Instructions] Next question comes from Jay Olson with Oppenheimer. Go ahead, your line is open.

This is [Sean] on the line for Jay. Thanks for taking the question. Congrats on the progress. Maybe like a two-part or two questions from us. First, we're just wondering if there's like a mechanism rationale to step forward behind the liver detargeting of the TRACER capsid and is this a way to further enhance the liver detargeting. And secondly, I'm just wondering for the ALPL binding, looking for new modalities. Curious about any particular modality you are thinking right now to prioritize? Thank you so much.

So I'll ask Todd to answer the first question and I'll take the second one.

Sure. So the first question was effectively mechanistically, why are capsids detargeted from the liver? And I can answer that in two parts. One, this is something that we're seeing with a variety of our different capsid families, and others have reported this too for capsids that cross the blood-brain barrier. It's an empirical observation that many of these capsids deliver to the liver less than they deliver elsewhere or less than the parental capsids do for those that don't deliver across the blood-brain barrier. As to the reasons why? We can speculate, some of it is, we know that subtle changes that affect the charge of the capsid can impact things like liver delivery. The other is, again, with relating to the empirical observations is that, we are choosing to move forward those capsids that already targeted from the liver. This is part of our selection criteria and something that we're specifically looking for to reduce the potential for any off-target problems.

And just a quick answer to the second question on ALPL. So you're correct, we are interested in using ALPL binding ligands and conjugating various macromolecules to them to see if we can get them across the BBB. And we're testing proteins such as therapeutic antibodies and enzymes. We're also going to be looking at whether or not they can transport oligonucleotides, both ASOs and siRNAs. And yes, we're doing those experiments now.

Thank you.

[Operator Instructions] Next question comes from Joon Lee with Truist. Go ahead, your line is open.

Hi. Good afternoon. This is Mehdi on for Joon. Congrats on the progress. Thanks for taking our question. So maybe a big picture question for us. Given time to data, especially in relation to TRACER platform, and also, recent advances in the field, basically, on decorated AAVs, how do you see the future of CNS-targeted AAVs in the next 12 to 18 months? And also, how you plan to ensure your leadership position in this space? Thank you.

That's an interesting question. And look, we have to be aware of the fact that there are multiple other companies pursuing the approach that I believe the Voyager scientists pioneered, and not just modifying the AAV, but as you just pointed out, decorating, if you will, AAV with, for example, TfR binding motifs. And so, those are all viable approaches potentially, but we don't know until we do the experiments in humans which ones will work. I would say that in the future, what we're going to see is, for example, the earlier question, what other tissues can you target besides the brain because several diseases involve more than just the CNS? Second is cell-type tropism. So it's not just the tissue, we want to target certain cells. And sometimes it's neurons, sometimes it's glial cells, sometimes it's oligodendrocytes. Sometimes it's a combination of those cell types. And then there's the detargeting, not only the liver, but also other potential cells of toxicity, such dorsal root ganglia neuron. So when you add all that together, I think there's going to be a need for multiple capsids that are going to be required for certain diseases. And that's why, as Todd said earlier, we developed capsid profiles for each of the diseases we're considering, and we have pretty high bar. Finally, I'd also say that there's other issues that we should remember, manufacturability, for example, and that's built into our development candidate criteria. There's immunogenicity, and there are potentially ways of affecting immunogenicity by making variations in the capsid. And so, I think there's still a lot of innovation to be had. But I also want to emphasize the fact that we may want to tailor the capsids to the disease that we need to treat and the cells in which that we need to get the transduction to occur in.

Thank you.

[Operator Instructions] The next question comes from the line of Sumant Kulkarni with Canaccord Genuity. Please go ahead, your line is open.

Good afternoon. Thanks for taking our question. So, on your anti-tau programs conceptually, what are the pros and cons of targeting extracellular versus intracellular tau? And with your gene therapy program, are you aware of any downsides of potentially one-and-done tau silencing approaches, given the role of tau in microtubule stabilization?

Well, maybe I'll start and then I'll ask my colleagues, either Todd or Toby to add. I would say that targeting extracellular tau is likely to be safer, as you're kind of implying in your question because you're not affecting all forms of tau and you're not affecting the intracellular tau in particular. But on the other hand, there are questions about efficacy, particularly given, as what Toby said, the N-terminal antibodies have failed. And so, there's that. And then in terms of the knockdown, we all know – first of all, tau knockout animals are actually pretty – they're viable, they actually can reproduce. And so, even though we think that there is a role for tau in during development, certainly, it doesn't seem to be – there seems to be some tolerance for the loss of tau. I'd say the other thing is that, we're fortunate in the sense that BIIB080 is going to enroll hundreds of patients into a well-controlled study. And we will have some idea of the safety actually over the long-term, because those studies were started a couple of years ago. So we should have long-term data on the safety of knocking down the expression of tau by the time we enter the clinic and start our journey ourselves. And then also in terms of the magnitude of knockdown, too. I mean, we'll have some idea perhaps by then as what is safe and what's not. Toby?

Al, I don't have much to add. I mean, I just think that the human data, in particular, the experience of maybe some of the genetic data really suggests that, at least as we understood so far, that knockdown tau has been well tolerated. Of course, we'll need to see the longer-term data. And I think it's sort of the idea that you – with knockdown supersede all forms of tau and really address tau in its totality is quite important. And for the antibody program, really, we have targeted the pathologic form of tau, and based on our spreading model, we think that is a very reasonable thing to do given the knockdown we've seen. And so, I think that's important. And we think they could be essentially complementary to each other.

I'll add just a little bit, although I think that the human BIIB080 data will ultimately supersede anything preclinical, I will add that preclinical studies to date, in addition to what Al described with the tau knockout animals has all looked remarkably benign. And so, people have looked in non-human primates as well as rodent species. We've done this internally in our mouse studies that we've talked about at conferences. Other people have reported on this. And so far, reduction of tau using gene therapy or gene therapy-like approaches has seen quite remarkably benign. So you never know until you do the ultimate human experiment. But to date, things look pretty positive with regard to knockdown risk.

Thanks.

[Operator Instructions] The next question comes from Yanan

Hi. Thanks for taking our question. This is Kuan on for Yanan. So I have a quick question on the siRNA program, sorry siRNA. So when may we see the NHP data? And you previously mentioned that there is a potential for combo strategy with the antibody. So any updated thoughts on that? And would you seek the approval of antibody first? Or would you synchronize the programs? Thank you.

I'll ask Todd to answer the first part of the question and Toby to answer the second part.

Yes. For the first part of the question, we have ongoing experiments to drive toward development candidate identification. We've given no guidance on when we expect to have those data. The guidance that we've given is that IND in 2026.

On the second part of the question, what I would say, you asked a question about synchronizing programs, I think fundamentally what's most important to the context is that, there remains a strong unmet need for people with Alzheimer's disease. And so, we certainly – if we had positive data for our tau antibody program, which of course is in the lead, we would move forward with that program.

Got it. Thank you for that. And a quick follow-up. So it's a hypothetical question for the antibody. So if you are able to stop all the spread of tau between cells, would that be enough to save the early-stage patients, such as Braak Stage II patients?

I think fundamentally, it's a very reasonable question. I think we would, of course, be elated if we saw that. I think what we understand from the spread of tau based on tau PET and tau pathology is that, is the intent of this program. We'll have to figure it out in the clinic.

Thank you for all the color.

The next question comes from Laura Chico with Wedbush Securities. Go ahead Laura, your line is open.

Thanks very much. And thanks for taking the question. Good afternoon. I wanted to ask two questions related to the GBA1 and the Friedreich's ataxia programs, just to mix it up a little bit here. Wondering if you could talk a little about the type of patients that you would be seeking to identify. And essentially, there have been a few other gene therapy efforts kind of ongoing in these spaces, but wondering how you think about what's the appropriate window for therapeutic intervention. Any color there. And then just one quick follow-up. Can you remind us about any potential remaining milestones that we should have on our radar for 2024? Thank you.

So I think for the Friedreich's ataxia programs, I'll remind that these are partner programs work and they own the development of that program. I think if you look to the other programs that have gotten approval, such as [indiscernible], they've looked at broad populations, both adult and some younger age patients. So I think fundamentally, that there is a path there that's been paved, but this really sits with [Nrf2]. And then the milestones, I think we just don't comment on milestones.

I would just say, also add that on FA, it's great that the first drug ever for FA was approved. The mechanism of action. It's an Nrf2 activator. I think it's going to be – I think our drug would only add to the efficacy. And so, because they're completely different mechanisms of action, ours is replacing frataxin. So I'll just say that. And then ask you to – Laura to ask a Neurocrine the more specific questions.

Okay. Thank you guys. Appreciate it.

You are welcome.