Voyager Therapeutics, Inc. Q1 FY2024 Earnings Call

Good afternoon, and welcome to Voyager Therapeutics First Quarter 2024 Financial Results Conference Call. Please note that today's conference is being recorded. A replay of today's call will be available on the Investors section of the company's website approximately 2 hours after completion of this call. I would now like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer.

Thank you, and good afternoon. We issued our first 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. Todd Carter, our Chief Scientific Officer. We will also be joined for the Q&A portion of the call by our Chief Operating Officer and Principal Financial Officer, Robin Swartz. Before we get started, I would 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. And now I will turn the call over to Al.

Thank you, Trista, and good afternoon, everyone. Please turn to Slide 3. I'd like to start by thanking the Voyager team for their dedication to creating transformative genetic medicines. We made tremendous progress advancing these medicines in the first quarter. We just announced that we have obtained IND clearance for our anti-tau antibody, VY-TAU01, for Alzheimer's disease, and we expect to announce the dosing of the first subject in a single ascending dose trial in healthy volunteers in the coming week or so. Our gene therapy pipeline also advanced during the quarter with development candidates selected in the GBA1 and Friedreich's Ataxia programs partnered with Neurocrine. These programs, along with our wholly owned SOD1-ALS program, are advancing towards IND filings in 2025. In March, we appointed Dr. Toby Ferguson as our Chief Medical Officer. Toby is an exceptional biotech executive with deep experience advancing novel therapies for CNS diseases, including tofersen, the first genetically targeted therapy to be FDA-approved for SOD1-ALS. Toby has hit the ground running, and we look forward to his leadership of our emerging clinical portfolio. In January, we announced an expansion of our relationship with Novartis through a new strategic collaboration and capsid license agreement to advance potential gene therapies for Huntington's disease and spinal muscular atrophy. This agreement, together with the public offering we completed in January, brought $200 million of total consideration to Voyager in the first quarter. This bolstered our balance sheet and extended our runway into 2027, which we expect will enable us to achieve multiple clinical data readouts. Finally, we presented a robust set of data at the recent AD/PD and ASGCT meetings, including data on our multiple tau-targeting programs and our second-generation capsids. Given this significant progress, we believe Voyager is emerging as a leader in neurogenetic medicine. Our pillars of value are summarized on Slide 4. First, we have a strong pipeline of 4 wholly owned and 13 partnered programs with the first expected to enter clinical trials in the coming weeks and the potential for 3 more to follow next year. Second, we have an industry-leading platform designed to overcome the delivery challenges inherent to CNS gene therapies. Our TRACER platform enables us to create novel capsids that, following IV delivery, harness the extensive cerebrovasculature to enable widespread payload distribution across multiple brain regions and cell types. These capsids have demonstrated translatability in multiple species and enabled the selection of multiple development candidates in our wholly owned and partnered gene therapy programs. Third, we have blue-chip partnerships anchored by TRACER's potential to transform the treatment of CNS diseases. In addition to Neurocrine, our partners include 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 nonviral 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.

Thank you, Al, and good afternoon. Please turn to Slide 5. This slide summarizes the 4 wholly owned programs and our 13 partnered programs that Al mentioned earlier. Part of what attracted me to Voyager is that these programs focus on targets validated by human biology and human genetics. As a drug developer and former practicing neurologist, I've dedicated my career to improving the lives of people living with neurologic diseases. While our understanding of the genetic and biological basis of CNS diseases has advanced considerably, translating that understanding to new therapies has been hindered by challenges with crossing the blood-brain barrier. I believe that the progress Voyager has made in this regard is transformative and provides an unprecedented opportunity to redefine the treatment of CNS diseases. I'm delighted to join the company as we prepare to enter the clinic and realize the full potential of our pipeline of neurogenetic medicines. Turning to Slide 6, I want to focus for a moment on 2 of our wholly owned programs that target tau. We believe tau is a critically important target for the treatment of Alzheimer's disease. The presence of tau pathology in the brain is a cardinal feature of AD. Further, the sped-up tau pathology through the brain closely correlates with clinical decline and can be visualized with tau PET imaging. Importantly, recent third-party clinical data generated using an intrathecally administered tau ASO have shown that reducing tau was associated with favorable trends on clinical outcomes. As Al mentioned, we're excited to announce that VY-TAU01, our anti-tau monoclonal antibody, obtained IND clearance. We look forward to announcing, in the coming weeks, the initiation of a single ascending dose trial in healthy volunteers. I'll talk more about that trial in a moment. First, a bit of background on this program. VY-TAU01 aims to inhibit the cell-to-cell spread of tau in the brain. In contrast to third-party anti-tau antibody approaches that have targeted the intrinsical and have been unsuccessful in the clinic, VY-TAU01 targets the specified epitope. We believe the epitope matters. In a preclinical in-vivo model of tau spread, the surrogate of VY-TAU01 inhibited tau spread by approximately 70%, while internally directed antibodies had no significant effect. We look forward to establishing whether or not it has positive predictive value as we advance into clinical trials. Importantly, and in parallel, we are progressing a tau silencing gene therapy approach intended to inhibit the production of tau protein. This program deploys a tau-targeted SRNA packaged into an IV administered TRACER capsid. Using this approach, we've demonstrated robust reductions in tau mRNA and protein across the brain by 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. We anticipate filing an IND in 2026. Turning to Slide 7, as I mentioned, we anticipate announcing the dosing of the first subject in our single-ascending dose trial for VY-TAU01 in the coming weeks. This will be a single-site study in which we expect to enroll approximately 48 participants. The primary aim of the study is to generate initial safety and pharmacokinetic (PK) data that will inform a subsequent multiple ascending dose trial. We expect to conduct the multiple ascending dose trial with participants with early Alzheimer's disease next year and generate initial tau PET imaging data in 2026 that has the potential to show slowing of tau spread. Turning to Slide 8. In addition to our programs targeting tau, we are also advancing 3 gene therapy programs for which we expect to file INDs next year. They include our wholly owned SOD1-silencing program targeting the genetic cause of SOD1-ALS, the Neurocrine partnered GBA1 gene replacement program targeting the genetic cause of Friedreich's Ataxia, and another Neurocrine partnered GBA1 gene replacement program. Mutations in GBA1 represent both one of the most common genetic causes of Parkinson's disease and the cause of other GBA1-related diseases. Each of these programs leverages an IV-administered, blood-brain barrier penetrating TRACER capsid and has the potential to provide a single-dose disease-modifying treatment. We look forward to advancing this promising suite of programs in the clinic.

Thanks, Toby. Please turn to Slide 9. In support of our advancing gene therapy pipeline, we were pleased to present a robust set of data on the potential clinical translatability of the manufacturing and overall performance of our TRACER capsids at the American Society of Gene and Cell Therapy Annual Meeting last week. Voyager scientists presented a total of 12 abstracts at the meeting, and I'd like to review a few highlights. First, we presented new data on our second-generation IV-delivered TRACER capsids. This session was standing room only with a line out the door and down the hall, which I think speaks to the high level of interest in novel capsids engineered to cross the blood-brain barrier. Our second-generation capsids should further enhance blood-brain barrier penetrability and reduce liver expression compared to our first-generation TRACE-derived capsids. These second-gen capsids demonstrated robust transduction of 50% to 75% of cells across diverse brain regions, with upwards of 95% transduction in certain key cell types, such as Purkinje neurons, at a clinically relevant dose of 3x10^13 vector genomes per kilogram. This also included transduction of 98% of dopaminergic neurons in the substantia nigra and over 80% of spinal motor neurons. Importantly, our TRACER capsids have enabled the selection of development candidates for the 3 lead gene therapy programs that Toby discussed. We presented data at ASGCT on VY-9323, our wholly owned SOD1-silencing gene therapy, which uses a second-generation TRACER capsid. The data demonstrated that a single IV dose of VY-9323 at the 3E13 vector genomes per kilogram dose reduced SOD1 mRNA by up to 80% in spinal cord motor neurons in nonhuman primates. Finally, as part of our strategy to mitigate the risks of developing TRACER capsid-derived product candidates and maximize their probability of success in the clinic, Voyager has been working to identify the receptors that mediate the delivery of these capsids into the CNS and confirm their expression in humans. At ASGCT, we identified tissue nonspecific alkaline phosphatase, or ALPL, formerly known as receptor X, as the highly conserved receptor expressed on brain vasculature that mediates the delivery of TRACER capsids VCAP-101 and 102 across the blood-brain barrier. These capsids bind to human, primate, and murine ALPL isoforms, further strengthening our confidence in the clinical potential of TRACER capsids. More broadly, these data establish ALPL as a novel brain delivery shuttle, and we are exploring the opportunity to leverage this receptor to deliver multiple therapeutic modalities across the blood-brain barrier. We look forward to sharing these data in the future. Collectively, the data package we presented at ASGCT represents the most extensive validation to date of the potential clinical translatability of our TRACER capsids. We look forward to evaluating their ability to transform the course of a broad range of neurological diseases.

Thanks, Todd. Turning to Slide 10. You can see Voyager has had an incredibly strong start to the year. As I mentioned before, this would not be possible without the hard work and dedication of our employees. I know many of them are listening, so I want to say, again, thank you. With a robust slate of upcoming clinical milestones, a maturing partnership portfolio, and cash runway into 2027, we believe Voyager is poised to drive significant value over both the near and long term. With that, we will open the call for questions. Operator?

Our first question comes from Joon Lee of Truist Securities.

Congrats on the great progress. This is Mehdi on for Joon. Last week at ASGCT, you showed great data related to Receptor X, ALPL. So could you please elaborate on the ways that you are planning to use this knowledge for the delivery of the other modalities to CNS? Specifically, do you think antisense oligonucleotides and LMPs could see similar levels of transcytosis as seen with AAVs?

Yes. Thanks for the question. So briefly, we know that these receptors mediate the transport of these very large AAV capsids across the blood-brain barrier. What we're going to do now is to make ligands against the receptor and conjugate them to various macromolecules to see if we can get them to cross the blood-brain barrier. We believe by transcytosis. The range of molecules we could look at includes protein therapeutics as well as oligonucleotides, and we're progressing those experiments as we speak. Todd?

Thanks, Al. So we are looking at a variety of modalities. As Al indicated, we're looking at antibodies, oligos, and other sorts of proteins. Al mentioned that we're in the process of identifying ligands, and we have identified some ligands. We're looking forward to hopefully sharing some of those data when we're ready.

Our next question comes from the line of Jack Allen of Baird.

Congratulations on the progress. I wanted to ask about some of the work you presented at ASGCT around the optimization of manufacturing. How are you thinking about optimizing manufacturing before you bring candidates into the clinic with your gene therapies? And what do you expect the benefits will be as it relates to costs of goods sold (COGS) of your more potent gene therapies as well?

Well, I'll start and I'll ask Todd to help here. So we're going to plan to use HEK293 cells to manufacture these products. We have a very robust internal technical operations team, and part of the development candidate selection is to assess manufacturability, both upstream and downstream processes. We're going to be verifying the percentage of full capsids, partially full capsids, and anti-capsids. So we assess manufacturability as part of the development candidate selection. Todd?

As Al mentioned, manufacturability is a key component. It's part of our whole assessment of our novel capsids as we identify them. Each case, the payload can make a difference, so for any given program, we have to establish the manufacturability with the capsid in question and the particular payload for the disease indication as well. All that goes into our assessment, and we begin with research-grade material. Once we develop the candidate, then we proceed to the process development to move that into manufacturability. You also asked a question about COGS. It's not necessarily a 1:1 trade-off, but you can imagine, as we're looking with our novel capsids that have a potency approximately an order of magnitude greater than the doses currently used in the clinic, we expect to see substantial savings because we need much less material to deliver the same level or even greater levels of delivery to the CNS than the conventional capsids.

Yes. I would just add, Jack, that in addition to the lower doses, we note that we're going to transfer the process to a CDMO for manufacturing. The CDMO world has come up to speed in terms of scalability. We're now seeing scale, and every time you increase the scale, we reduce the cost. So at the pace that it's growing, we expect to see continued advancement in that area as well.

That's great. Can I just ask one final question on that? I know we haven't really gotten this far in the gene therapy space, but how does the shelf life of these products play a role when you think about the commercial applicability of this manufacturing scale here?

Shelf life. Wow, that's a question I hadn't thought about yet.

We do assess the shelf life. For a gene therapy, we typically would need to be held at particular cold temperatures. All that is part of the evaluation for stability, both short term and long term. So that's an important part of our manufacturability and our process development.

Our next question comes from the line of Patrick Trucchio of H.C. Wainwright & Co.

Congrats on all the progress. Just a couple of follow-up questions for me. The first is, I'm wondering if you can discuss any potential read-through that you'll be looking for from the advisory committee meeting on June 10 regarding donanemab in Alzheimer's disease to your Alzheimer's programs. And then separately, just a follow-up on the ASGCT data, specifically the data in the human tau mouse model that showed reduction in tau mRNA levels up to 90% and a 50% to 70% reduction in tau protein. Can you tell us how this data compares with prior-generation capsids and how the data may support the advancement of the tau silencing gene therapy IND in 2026?

Thanks, Patrick. I'll answer the first question, and maybe I'll ask Todd to answer the second one. On the first question, it will be a very interesting advisory committee. We do have a vectorized anti-amyloid program in our pipeline as well, so we're watching that advisory committee with interest. I think a lot of the questions might be unique to donanemab and may not pertain very much to our program. Nevertheless, there might be some important features, for example, what are the outcomes that are going to be important for approval. Of course, that's always something that we need to keep an eye on, but that's down the line for us. We have to get into the clinic first, but that's the kind of thing we may be paying attention to, but it will be an interesting meeting. Todd?

On our tau knockdown program, the data that you're referring to, we showed some at AD/PD and also at ASGCT. The knockdown in the mouse was with a mouse-capable capsid, used to assess the payload, and hopefully demonstrate that the payload has the ability to knock down tau, both mRNA and protein at a clinically relevant dose. We think that, that's what we showed in those mouse studies. With regard to the payload, we were able to see a well-tolerated and safe dose in those animals, delivering sufficient vector to the brain, and we saw a quite remarkable knockdown of the mRNA in those animals. So it's building that proof of concept for knockout, and we're moving forward now and evaluating the novel capsids for nonhuman primates and humans with the payloads in question. So we're looking forward to sharing more of that in the future.

Our next question comes from the line of Philip Nadeau of TD Cowen.

Congrats on the progress. First, a couple on VY-TAU01. Have you disclosed what doses you are going to be exploring in the single ascending dose trial? And can you talk a little bit about how you're going to use the pharmacokinetic data that you gathered to determine what doses should be explored in the multiple ascending dose (MAD) trial? How will you extrapolate from the single dose to the multiple doses and particularly for brain peripheral versus maybe crossing the blood-brain barrier?

Thanks for the call. This is Toby. We haven't disclosed our doses, but broadly speaking, we've examined our candidates in our preclinical model of tau spread, where we've shown that we see reduction by about 70% of the spread of pathologic tau in our mouse models. In addition, we've done preclinical work in primates. This is a single ascending dose study in about 48 patients over multiple cohorts. We expect, based on that data, to get both, of course, safety information as well as PK information on BBB that we think we can appropriately translate into doses for the multiple ascending dose study in mid-2025, whether we want to aim to estimate the underlying exposures needed to get appropriate exposure in the brain to treat this.

Yes. And Phil, I may want to add that based on our preclinical studies, including NHP models, we don't want to anticipate any major surprises. This is likely to be very similar to other monoclonal antibodies, and therefore, the brain-to-plasma ratio will be in the 0.1% to 0.5% range. As Toby said, we know the exposures that we need to get into the brain to inhibit tau spreading in the model that we used to choose the antibody. So that will give you some idea, and of course, we do expect that trial to inform the dose range in the upcoming MAD trial.

That's really helpful. And then second, on the frataxin candidate, would you be able to disclose anything new about the candidate that was chosen? And anything notable that you'd be willing to tell us about what differentiated that candidate from the others?

Well, so that's a Neurocrine program. We don't want to disclose these things. Suffice it to say that the development candidate we had a set of criteria for the capsid as well as the capsid-plus-payload combination, both in terms of its mechanistic effects in animals as well as manufacturability. We'll ask Neurocrine to answer your question.

Congrats, again, on the progress.

Our next question comes from the line of Ry Forseth of Guggenheim Securities.

From the ASGCT data, now with generation-3 technology maturing, where you're able to navigate preexisting neutralizing antibodies, how are you framing the market opportunity expansion given the preclinical profile you're seeing to date?

I'll start, and maybe Toby or Todd can add. Yes, so you noticed that our one of our posters that we are leveraging TRACER to see whether we can make modifications to capsids that affect immunogenicity. By that, what we're doing is we're looking to see whether preexisting antibodies in humans can affect the capsids, and therefore, affect their performance in the clinic. Obviously, if we can find novel capsids that can evade preexisting antibodies, more patients would be available for treatment.

I would agree with Al. The only point I would make in addition is that this may be particularly important in adult populations that may select pediatric populations where there's not as much concern. That may represent some opportunities.

Our next question comes from the line of David Hoang of Citigroup.

First, I wanted to ask how you view the anti-tau antibody's role in the Alzheimer's treatment landscape in relation to the tau silencing gene therapy you have. What are the advantages and disadvantages of each approach? Additionally, have you explored other transporters besides ALPL for crossing the blood-brain barrier? If so, how does ALPL compare to those other transporters?

I'll start on the first question, and then Toby, I'll ask Toby to help with that one. Todd, maybe you can answer the second question. So anti-tau versus tau silencing are very different approaches. The anti-tau, we expect to bind the extracellular forms of tau. As Todd said earlier, we're trying to block the spread of pathological tau, which we've demonstrated quite nicely in an animal model. The tau knockdown is a very different mechanism of action. It will need to be given on a regular basis, probably on the order of every month or so. The tau knockdown is gene silencing that will be done by gene therapy, a once and done, essentially. It decreases the expression of all forms of tau and is akin to others that have used an antisense approach to decrease tau expression, so it's different. We'll have to see the first thing is which one works the best and whether or not it can be done once and done or whether it will require regular infusions.

Thank you, Al. I think what I would add is that we fundamentally, at this point, don't have enough clinical data to understand the potential completeness of treatments with either with any of these modalities. The most important point is determining which ones work. We're excited to test have 2 opportunities to test tau in our programs, both the antibody program and the knockdown program. I do think moving forward, we'll need to look and try to understand the combination as well, and that is potential to be investigated in the future.

Todd, do you want to take the second question?

Sure. The second question, just to recap, would be the evaluation of ALPL in the context of other potential shuttles or shuttle targets for BBB delivery. We absolutely would need to evaluate ALPL in the context of other receptors, such as transferrin, and there are a few others. While we're not in a position to share any data today, anything we would choose to move forward would need to perform at least as well as the existing BBB transporters, and that would be part of our assessment and evaluation. Looking forward to hopefully sharing more about our work in that area.

I think David was also asking whether we have other receptors and how we're looking at those compared to ALPL.

We have identified some other receptors. We have multiple capsid families that target different receptors. In terms of our novel receptor discovery, we have identified a few, and we are in the process of evaluating all of them for nonviral delivery.

Our next question comes from the line of Jay Olson.

This is Chung on the line for Jay. Congrats on the progress. Maybe a 2-part question on the ALPL program you've disclosed. Just first, I'm just wondering if you can talk about the expression variability of ALPL in humans and maybe whether the expression may change over time with aging or underlying diseases. And secondly, for the development of other therapeutic modalities or delivery modality using ALPL, are you planning to do that internally or through collaborations?

So Todd will answer the first question. I'll answer the second one.

On the first question, regarding changes in ALPL expression, we can look at different genetic variations of ALPL and we're in the process of doing that. ALPL is expressed robustly starting at birth, and that expression goes up a bit with age. We might expect better delivery in older populations, but evidence thus far suggests that the level of expression in the vasculature is quite robust, even starting very early.

In terms of the second question, we expect to be doing a lot of the work internally, and we already have started to do that. But we're always looking for collaborations that can enhance that discovery and development efforts. So stay tuned.

Our next question comes from the line of Sumant Kulkarni of Canaccord Genuity.

Nice to see all the progress. I guess these are welcome questions for Dr. Toby Ferguson. So on your SOD1-ALS program, given the limited patient population and because tofersen is already on the market, do you expect to involve tofersen in preclinical work? And how do you expect eventual trial recruitment to play out for your SOD1-ALS program?

Thanks for the question. Fundamentally, tofersen is approved and is a disease-modifying therapy for ALS. What I would point to on our programs... Yes, once a month.

Once a month.

What I'd highlight at ASGCT is really the transduction data. In motor neurons, we saw 80%-93% transduction and up to 6%-8% in the cortex with second-gen VCAP capsids. That's quite important. In the context of our VY-9323 program, we saw a 72% reduction of SOD1 mRNA and 80% in the core. So fundamentally, we'll take some lessons from tofersen, particularly around biomarkers for our clinical development program. We think this provides us an opportunity to understand the potential proof of concept in people with ALS, along with the potential importance for our TRACER platform.

If we look forward to the potential approval of our SOD1 gene therapy, in the case of SMA, SPINRAZA was approved a couple of years prior to Zolgensma. The two are used concurrently in the real world. Many patients can get treated with Zolgensma right after birth and then add SPINRAZA if necessary. Taking gene therapy doesn't preclude continued treatment with patients when necessary. If we take a page from the SMA story, we could see both products used to treat patients optimally.

Got it. As a quick follow-up, what percentage reduction in neurofilament light (NFL) levels is considered clinically relevant in the SOD1-ALS context? We've seen the data that Biogen had. What would be considered clinically relevant, I guess, for what's out there already and for a gene therapy?

We've all seen the reductions that Biogen has highlighted with neurofilament reductions. What a clinically relevant reduction is not clear. It has to be substantially greater than the variability of your assay and biological variability. The tofersen data does inform the magnitude of needs for reduction.

Our next question comes from the line of Yanan Zhu of Wells Fargo Securities.

First, I was wondering about the ALPL receptor. Is there expression of this receptor in any other tissue? And how does that potentially impact or not impact a brain delivery drug in terms of delivery into other tissues?

Sure, this is Todd. ALPL is expressed across the vasculature and the entire body and in some other cell types. However, AAV capsids do not need to harness these other mechanisms to get into other tissues. But the blood-brain barrier is blocking for most conventional capsids to get into the brain. The harnessing of ALPL to cross the blood-brain barrier is really only important to get into the brain. What we also see is that using ALPL is giving us some significant cross-species activity. We have examples of four species: African green monkeys, cynomolgus macaques, marmosets, and mice. At relatively low doses, we're able to achieve high delivery and transduction - 80% of motor neurons in the spinal cord, 95% in Purkinje neurons, and 98% of dopaminergic neurons in the substantia nigra. Finally, we see a significant de-targeting from the liver. That targeting is likely not driven by ALPL specifically, but probably based on other characteristics of the capsid.

Great. That's very nice to hear. Also, at ASGCT, there were quite a few presentations on BBB penetrating capsid work from different industry players. Some began to touch upon receptors. I think you might have started a trend. After surveying the landscape, how do you feel about your BBB capsid and where it stands in the landscape?

Maybe I'll start and Todd will complete the answer. It's great to see that a lot of people are finding what we found years ago. The world appreciates the need for new capsids that cross the blood-brain barrier to improve delivery. The competition is heating up. We are very proud of our capsids. As Todd mentioned, we target key cells relevant for the diseases of interest. We get 80% to 90% of cells transduced at relatively low doses, and we have demonstrated multiple cross-species experiments.

The three candidates we're moving into the clinic tomorrow represents a significant next step for us.

Our next question comes from the line of Laura Chico of Wedbush.

Just one housekeeping question. I believe there was one milestone payment triggered in the second quarter. But curious if you could elaborate or if you've disclosed any additional milestones that we should be watching for over the remainder of 2024? I have a quick follow-up for you.

Thank you for the question. We were very pleased with the advancement of our Neurocrine programs and the achievement of the DC milestone. However, we don't provide guidance on potential future milestone payments across our 13 partner programs. It is also important to note that further milestone payments are not included in our cash guidance, which is into 2027.

Okay. In terms of the follow-up, there's a lot of discussion on the ALPL receptor data, but I'm wondering, perhaps, Al, strategically, what would happen in terms of the focus for Voyager with the VY-TAU01 data. If that reads out positively in patients, what does that mean strategically for focus? Since that's as an antibody right now, how would that shift or change the focus on other TRACER programs, assuming success?

Thanks for the question, Laura. What you're implying is that we would have a choice of whether we proceed with the VY-TAU01 program as an intravenous antibody or whether we could vectorize the antibody. We have that option. We may actually do both, in fact. I've always been thinking that strategically it wouldn't make sense for Voyager, a small company like us, to try to go into Phase III or commercialize in Alzheimer's disease as it's too large and too expensive. So we've always thought we will likely get a partner if the VY-TAU01 program is positive, but the ability to potentially vectorize a once-and-done antibody could be of high interest to us, and we'll make that decision when the time comes.

Our next question comes from line of Joon Lee of Truist Securities.

Following Laura's question, last week at ASGCT, BioPharm suggested in some presentations that compared to capsid and inserted vectorized antibodies, the expression of capsid and inserted vectorized antibodies had a lower expression. Do you expect the same for your vectorized antibody platform in general and specifically for the Alzheimer's antibody? If you could share any plans that you have for preclinical data in this program?

Yes. Let me start, and then I'll ask Todd to help. When we vectorize an antibody, we showed at a meeting that we can vectorize an anti-amyloid antibody and get enough expression to bind to amyloid plaques in transgenic mice. My view is that a lot is going to change relative to IV. We're going to lose the Cmax, high concentrations that you get immediately after IV dosing. We expect to have more constitutive expression from within the central nervous system. We expect that we'll have mainly glial cells producing the antibody. And then we would be able to look in animal models at not only binding to amyloid plaques, but we will assess whether we can lower amyloid plaques. There are precedents we can follow in vivo studies with the anti-amyloid antibodies.

While the VY-TAU01, the focus is on the antibody itself, not on a vectorized form. We do have substantial experience going back several years on vectorization of antibodies, including the anti-amyloid antibodies. The structure of the vector payload, the vector genome, and of course, the promoter can make a considerable difference. There are things we can do to tweak expression level, not just on the promoter, but by the kinds of cells, the specific cell types that you target. We'll be looking at all of those characteristics when we move forward with any vectorized form of an antibody.

I would also add that being able to give a vectorized anti-amyloid once IV and not have to give it every other week or every month could relieve the strain on the healthcare system with antibody treatments for Alzheimer's disease.

Very helpful. If I can sneak in one last question. Between now and the second half of 2026, where you hopefully present PET imaging data or VY-TAU01, how should we think about the cadence of any interim data releases related to your findings along the way?

I think what we've highlighted for the SAD program will inform the MAD program. The key data readout in that timeframe is in the latter half of 2026.

Thank you. I'm showing no further questions at this time. I would now like to turn it back to Al Sandrock for closing remarks.

Thank you, everyone, for joining us today. Feel free to follow up directly with any questions. Thanks again. Bye.

Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.