Good day, and welcome to Voyager Therapeutics Second Quarter 2022 Conference Call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this call which will be recorded. I would now like to turn the call over to Julie Burek, Vice President of Finance at Voyager.

Thank you, operator. Good afternoon, everyone, and welcome to this conference call to discuss our second quarter 2022 results and prioritized pipeline. A replay of today's call, including the Q&A, will be available on the Investors section of our website approximately two hours after completion of this call. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that 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. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC and as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements even if our views change. I'm joined today by our Chief Executive Officer, Dr. Al Sandrock. For the Q&A portion of the call, we will be joined by our Senior Vice President of Research, Dr. Todd Carter. Now I will turn the call over to Al.

Thanks, Julie, and good afternoon, everyone. I'm extremely pleased to discuss some exciting new developments at Voyager. Voyager's mission is to pioneer the discovery of transformational AAV capsids that we hope will enable the development of life-changing gene therapies. We believe that the novel capsids derived from our proprietary tracer platform represent the breakthrough innovation that will address certain fundamental limitations that currently hamper gene therapy. We and our partners plan to leverage these capsids to advance the field of gene therapy for the central nervous system as well as other organs. We believe that our ongoing collaborations involving the TRACER capsids, including those recently signed with Pfizer and Novartis are progressing well. Both have option exercise milestones coming up in the next several quarters. Soon after joining the Company as CEO earlier this year, I led a comprehensive process to evaluate Voyager's R&D programs and determine where to focus with the goal of creating important new therapies for patients and growing shareholder value while maintaining our cash runway into 2024. Today, we are excited to announce our prioritized development pipeline, which builds on advances we've made with our TRACER capsids. Gene therapy has the potential to transform the treatment of many serious CNS diseases. A clear example of this is the transformational impact that Zolgensma had for the treatment of infants with spinal muscular atrophy. However, the FDA label limits the use of Zolgensma to those up to age two. The blood-brain barrier appears to preclude the use of intravenous gene therapy in older children and adults. Consequently, delivery methods such as the direct injection of gene therapy into the cerebral spinal fluid or CSF space or into the brain parenchyma have been and are being attempted. On Slide 5, we show examples from the published literature of what happens when these delivery methods are used in nonhuman primate experiments. We believe the situation is analogous when similar methods are employed in humans. An example on the left panel on this slide comes from a published study in cynomolgus monkeys, in which AAV9 expressing green fluorescent protein, or GFP, is injected intrathecally into the CSF space at multiple spinal levels. As you can see by the number of green-stained cells, there is a clear drop-off in the number of transduced cells as you go from the lumbar spinal cord to more rostral levels and even less in the brain, where there are a few weakly stained cells in patchy areas of the cerebral cortex and other regions. Injections into other CSF spaces, such as the cisterna magna, are not likely to be much better. Clearly, for most CNS disease applications, this pattern of distribution and low transduction efficiency is a major limitation and likely precludes significant clinical benefit. The panel on the right comes from a published study in which AAV5 expressing GFP was injected directly into the brain parenchyma. In this case, the putamen by means of a surgical procedure. GFP expression, as seen here by the brown staining, is highly localized to the site of injection. Intraparenchymal injections, even with convection-enhanced delivery, result in highly localized distribution. Moreover, although some CNS diseases may begin in the deep gray structures of the brain, most eventually involve the entire brain, so the limited distribution of gene therapy that is likely to result from such localized delivery methods imposes severe benefit-risk limitations for therapeutic utility. As these limitations became increasingly clear over the past several years, Voyager scientists believed that we could do better. We set out to discover novel capsids with improved tropism as a potential solution to the delivery and distribution challenges. We invented an approach now known as TRACER, which has resulted in capsids that in nonhuman primates have been shown to transduce CNS tissue far more efficiently after IV delivery than any conventional AAV capsid in use today. At the core of TRACER is our proprietary expression-driven in vivo screening platform. This platform has enabled our scientists to identify novel capsids that preferentially target the CNS and other tissues of interest. TRACER has allowed our team to evaluate more than 20 million variants of AAV5 and AAV9 capsids and select only those capsids that display increased transduction in the target organ. This approach has two distinct advantages. First, we performed the initial screening along with a series of subsequent screens in nonhuman primates, so we're selecting for capsids that show improved tropism in species very closely related to humans, not capsids that may only show activity in mice, which past experience has taught us may not translate well to other species, let alone human beings. Second, we measure the performance of our capsids at each step of the screening process by evaluating gene expression at the level of messenger RNA. When we measure the production of the desired mRNA in the target tissue, we have confidence that we are selecting capsids that not only get across the blood-brain barrier but that also enter into cells and deliver and express their payload productively. The results from TRACER have been remarkable. Our capsids have displayed more than 100-fold higher transgene expression in the brain as compared to the conventional AAV capsid in nonhuman primates. Slide 7 highlights some of what we have observed thus far with the novel capsids derived from TRACER. We have found that our novel capsids can efficiently target numerous therapeutically relevant regions of the brain, including the cerebral cortex, hippocampus, and spinal cord after IV delivery. At the cellular level, these capsids can efficiently transduce neurons, glia or both cell types. Remarkably, while our capsids increased targeting of neurons and glia in the CNS, at the same time, they can also de-target cells that may result in toxicity, such as liver cells and dorsal root ganglion neurons. Finally, we've also found that our capsids have improved CNS tropism across species, such as the macaque, the marmoset, and the mouse, which we believe improves the likelihood of translation into humans. In summary, we believe our data demonstrate that we can identify truly unique AAV capsids with the potential to enable promising therapeutic candidates for many CNS diseases that could not be adequately addressed using the currently available conventional AAV capsids. We're also very pleased to announce today that we have recently identified a receptor for one of our most promising TRACER capsids. We plan to provide further details on this finding in an upcoming scientific conference. What I can tell you today is that we have strong data supporting the identification of a binding receptor for one of our capsids, including data that show that our capsid binds to the human isoform of the receptor, which is expressed in brain endothelial cells and other CNS cell types. We believe that the characterization of this receptor-capsid interaction further increases the probability that this capsid will cross the blood-brain barrier in humans. Importantly, this discovery may provide a path for the rational design of IV-delivered BBB-penetrating capsids. Moreover, experiments are now underway to explore the possibility that this receptor may enable the CNS delivery of other therapeutic modalities such as proteins, antibodies, and oligonucleotides. I've discussed how our TRACER platform has resulted in the generation of capsids that we believe can overcome some of the most pressing hurdles facing CNS gene therapy and have tremendous potential to treat human CNS diseases. We are now combining these unique TRACER capsids with our team's deep knowledge of CNS disease biology and drug development with the aim of developing therapies against well-validated targets with potentially transformative clinical impact. I will now discuss our pipeline. Before doing so, I'd like to tell you how we prioritize the pipeline. First, we chose diseases with high unmet medical needs, serious life-threatening diseases where patients have few, if any, treatment options. Second, we chose well-validated targets for these diseases, those validated by human genetics and human clinical pathologic data that indicate that we are dealing with targets in disease-causing biological pathways. Third, we selected programs where it would be possible to rapidly and efficiently establish proof-of-concept or at least proof of biology in early-phase clinical trials. Fourth, we chose programs where we had evidence of robust preclinical pharmacology. And finally, we focused on programs that should provide meaningful commercial opportunities. Based on these criteria, three programs are now our top priorities: GBA1 gene replacement for Parkinson's disease, SOD1 gene silencing for SOD1-mediated ALS, and anti-tau passive immunotherapy for Alzheimer's disease. We will focus today's pipeline discussion on our prioritized internal programs and our plans to advance each toward clinical development. We note that in addition to these prioritized programs, we will also continue to conduct early research on gene therapy for Huntington's disease and vectorized HER2 antibodies. We hope to be able to advance these programs into later stages of research one day in the future. Let's now review each of our prioritized internal development programs in more detail. I'll start with the GBA1 Parkinson's disease program. Parkinson's disease is the second most common neurodegenerative disease, impacting about 1 million people in the U.S. alone. Up to 10% of Parkinson's disease patients have a mutation in GBA1, the most common genetic risk factor, decreasing the risk of the disease approximately 20-fold. GBA1 encodes the lysosomal enzyme, glucocerebrosidase or GCase, which degrades glycosphingolipid substrates. Homozygous loss of function GBA1 mutation results in Gaucher's disease, a lysosomal storage disease and heterozygous loss of function GBA1 mutations results in an increased risk of Parkinson's disease. Loss of function of GCase leads to the accumulation of glycosphingolipid substrates and alpha-synuclein aggregates, which are thought to be toxic to neurons. We hypothesize that the restoration of GCase in patients with Parkinson's disease with GBA mutations will have therapeutic benefit. The restoration of GCase may also benefit patients with idiopathic PD, where there is evidence of loss of GCase in the substantia nigra even in the absence of GBA1 mutations. Moreover, there is growing evidence of lysosomal dysfunction in general in idiopathic Parkinson's disease. As shown on Slide 13, on the left panel because of loss of function mutations in the GBA1 gene, there is reduced GCase activity in the relevant brain regions of patients who had Parkinson's disease or dementia with Lewy bodies who are GBA carriers. Interestingly, as mentioned earlier, there's evidence of reduced GCase activity in the substantia nigra even in PD patients who do not have GBA1 mutations, relative to control patients. Consequently, as shown on the right panel, substrates for the GCase enzymes such as glucosylceramide are elevated in the cerebral spinal fluid in PD patients who harbor the GBA1 mutation. This provides an opportunity to demonstrate proof of biology in an early phase clinical trial. If our gene therapy restores GCase enzyme expression in the brain, substrate levels in the CSF should fall to normal, providing a potential path to early clinical development de-risking. In a preclinical study presented at the ASGCT meeting this year, Voyager Sciences showed that an IV delivered gene replacement therapy in rodents increases GCase protein and enzyme activity in the brain and thus lowers the level of both glucosylceramide and glucosylsphingosine in the brain in a dose-dependent manner. This is shown on Slide 16. We hope to achieve similar results in the clinic with one of our TRACER derived capsids, and we are moving this program forward as shown on Slide 17. We are evaluating TRACER capsids in anticipation of selecting an IV delivered capsid for this program by year-end. In the first half of 2023, we expect to finalize selection of a development candidate. Following that, in the second half of 2023, we expect to initiate a dose-range finding study in nonhuman primates, and we anticipate initiating GLP toxicology studies in 2024. This timeline puts us on track for an IND in 2025, but we are actively reviewing options to accelerate the program. Moving now to SOD1-ALS, amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease that typically leads to death approximately three years after diagnosis. Current treatments are minimally effective, and there is a great need for improved therapies. Autosomal dominant superoxide dismutase one mutations are thought to cause a toxic gain of function that leads to the degeneration of motor neurons along the entire length of the spinal cord, the brain stem, as well as the upper motor neurons in the cerebral cortex. We believe that by reducing the expression of SOD1 in the central nervous system, we can provide therapeutic benefit to ALS patients with SOD1 mutations. From a clinical development standpoint, the ability to demonstrate reduced levels of SOD1 in the CSF as a target engagement biomarker, as well as the ability to measure plasma neurofilament light chain as a surrogate biomarker of clinical efficacy, greatly facilitates clinical development. Our therapeutic approach for SOD1 ALS combines a potent siRNA construct with a CNS-tropic BBB-penetrant capsid. Because of the potential for broad CNS targeting, we hope to address all of the major disease manifestations, involving the entire neuraxis, namely the brain, brainstem, and spinal cord with an IV delivered TRACER derived capsid. Preclinical data that were presented at the ASGCT conference earlier this year, shown on Slide 20, demonstrates that IV delivery of siRNA gene therapy leads to robust SOD1 knockdown in all regions of the spinal cord and significant improvements in motor performance, body weight, and survival in the G93A SOD mouse model. We believe these data provide preclinical pharmacologic support for our approach, and we are eager to advance toward the clinic. Slide 21 shows the anticipated milestones for this program, which are as follows: our NHP capsid evaluation study is underway, and we expect to select the final candidate by the end of this year. We plan to obtain a nonhuman primate dose range finding study readout in 2023, and we anticipate initiation of GLP toxicology study in the first half of 2024. If we achieve these milestones in a timely manner, an IND filing in the second half of 2024 is anticipated. I'll now transition to our passive immunotherapy program targeting tau. This program is based on research conducted by our team since the earliest days of the founding of our company. Our tau antibody discovery work for vectorization led to the discovery of novel antibodies selectively targeting pathological tau. These antibodies have a number of favorable characteristics supporting continued development. These include high affinity for pathological tau, a protein that has been linked to a number of neurodegenerative diseases, including Alzheimer's disease. Robust efficacy in animal models of tau spread. We are careful to differentiate from other anti-tau antibodies, including those that have been shown to be clinically ineffective. We plan to first leverage an anti-tau antibody as an IV immunotherapy. This approach has the potential to lead to high-value clinical candidates for the treatment of Alzheimer's disease and other tauopathies with tremendous unmet need. It may also lead the way for an eventual vectorization of these antibodies as gene therapy candidates. Some important advantages of this approach from a development standpoint are that immunotherapies with IV administration have already been shown to produce important effects in the brain and neurodegenerative diseases such as Alzheimer's disease. Moreover, we plan to use tau PET imaging which should allow for the rapid and efficient demonstration of proof of biology in an early phase clinical trial. We've known for some time now that tau pathology propagates across certain brain regions in a stereotype fashion in Alzheimer's disease as demonstrated by the seminal work of others. Those investigators have pointed out that the accumulation of tau pathology correlates better with dementia than any other biomarkers. Modern PET imaging studies, for example, have also shown that the spread of tau pathology correlating with increased impairment and advancing disease stage. In recent years, several controlled trials of amyloid-directed therapies have demonstrated the feasibility of evaluating the spread of tau pathology and longitudinal assessment of tau PET images in patients with mild cognitive impairment due to Alzheimer's disease over the course of 12 to 18-month trials. Our therapeutic hypothesis is that an antibody targeting tau may block the neuron-to-neuron spread of tau at several plausible extracellular sites, and that this may attenuate the progression of diseases such as Alzheimer's disease. Tau has been the target of several monoclonal antibodies, including those that have not demonstrated clinical efficacy. We are well aware of these studies, and we're careful to differentiate from these antibodies by targeting a different epitope. The Voyager antibody targets the C-terminal, which, to our knowledge, has not been tested in a well-controlled efficacy trial of tau immunotherapy. Slide 26 shows that our antibody in a relevant pathological tau spreading model is also differentiated in terms of biological activity from an internal antibody that has been equivalent to one that has failed to show efficacy in a Phase II clinical trial. In this animal model, pathological tau—called paired helical filament tau—is extracted and enriched from brain tissue from Alzheimer's disease patients. This material, called EPHF, can be injected into the hippocampus of the P301S mouse, a mouse strain that expresses a mutant human form of tau where it induces substantial formation of pathological tau. This pathological tau also spreads to and accumulates in the contralateral hippocampus. In our studies, we began dosing mice with antibodies for one week, injected EPHF, continued antibody dosing afterward, and sacrificed the animals six weeks later. Levels of pathological tau accumulation were then measured in the ipsilateral and contralateral hippocampus. There was a significant reduction of tau pathology in both the ipsilateral and contralateral hippocampus. In contrast, the terminal antibody IPN002 has been shown to be ineffective in a very similar mouse study. Of note, the IPN002 antibody had been humanized and, when tested in the clinic, failed to show efficacy in a Phase II clinical trial. As a result of experiments such as these, we believe that the Voyager antibody by targeting the C-terminal may have an advantage over N-terminal targeting antibodies in blocking the spread of pathological tau in the brain. We are advancing our anti-tau immunotherapy program toward the clinic and humanization of our murine antibody is already underway. Looking ahead, we anticipate selection of a development candidate in the first half of 2023, followed by initiation of GLP toxicology studies later that year. If we achieve these milestones in a timely manner, we would target IND filing in 2024. I'll now pass the call to Julie to review our financial results.

Thank you, Al. As we've previously announced, we have executed two important deals with Pfizer and Novartis, two global leaders in gene therapy for the application of our capsids for certain specific diseases. These deals have provided Voyager with meaningful nondilutive capital and have the potential to result in substantial additional milestone and royalty-based revenue. We believe both the Pfizer and Novartis have been progressing well with our teams collaborating closely. Looking ahead, we anticipate the Pfizer option exercise decision by October 2022 and the Novartis option exercise decision by March 2023. I'd also note that Voyager has ongoing partnership with Neurocrine Biosciences on a preclinical Friedreich's ataxia program and two undisclosed discovery programs. We are optimistic about the potential to enter into additional TRACER capsid collaborations with the goal of further leveraging our TRACER technology in partnership with other pharma companies. And in doing so, potentially helping to bring important new medicines forward. I'll now turn to our financial results. In the interest of time, I'll focus on a few key metrics. Voyager is in a strong position as we advance our platform and portfolio forward. We reported cash, cash equivalents, and marketable securities of $148.1 million as of June 30, 2022. Based upon our current operating plan, we expect that existing cash, cash equivalents, and marketable securities will be sufficient to make planned operating expenses and capital expenditures into 2024. Please see our press release and SEC filings for further details on our financial results. I'll now pass the call to Al for concluding remarks.

Thank you, Julie. Before I get to my concluding remarks, I'd like to welcome Catherine Mackey to our Board at this pivotal time in Voyager's evolution. Catherine's outstanding track record of R&D success, coupled with her vast expertise and strategic collaborations with industry partners will be invaluable to Voyager as we advance our pipeline and maximize our TRACER capsid discovery platform. I joined Voyager because I'm optimistic about our ability to make a meaningful impact on the lives of patients. I believe that the potential of gene therapy is enormous, but the challenge of delivering these therapies safely and effectively to the central nervous system as well as other organ systems has limited its utility to date. I believe our novel TRACER capsids can address some of these limitations and provide an opportunity for us and our partners to advance differentiated programs toward the clinic. The demonstration that our TRACER capsids have improved target organ tropism across species, combined with the very recent identification of the receptor for one of our promising capsids, gives us additional optimism that our capsids will offer the potential for improved tropism in humans. Our ongoing collaborations are going well, and there are upcoming license option exercise dates, including with Pfizer in October of this year. We're also optimistic about other potential collaborations in the future, given the promise offered by the novel capsids derived from TRACER across multiple disease areas. Our prioritized pipeline includes differentiated programs against validated targets for diseases of high unmet need, featuring strong preclinical pharmacology as well as clinical development plans with efficient paths to human proof of biology. We look forward to updating you about the progress on our science, our pipeline, and our partnerships in the coming months. Thank you for listening. We'll now open it up for questions.

The first question comes from Jack Allen with Baird.

Congratulations on all the progress in the prioritization of the pipeline. Maybe first, at a very high level, I was hoping you could provide some more context around the three assets that you plan to move forward. Maybe characterize the derisked nature of each of the assets and maybe the riskiness of, put another way, each of the assets. And then I have a follow-up as well.

Jack, this is Al. Thanks for the question. I'm not sure I heard the first part clearly. I know I heard the risky nature, but what was the first part of that?

I just asked how to de-risk, or maybe view each of these candidates if you could think about the overall risk profile of each of the assets.

Yes. Look, these are high risk, high reward, right? I mean because we're tackling diseases with high unmet need. But we feel we can manage the risk because we chose programs deliberately where we could derisk early in clinical development and efficiently. So for example, in the case of the tau program, we feel we can use tau imaging to see whether or not we can block the spread of tau in a very efficient manner in early-phase clinical trials, perhaps even in a Phase Ib trial in a matter of, say, 12 months. And in the case of SOD1 ALS, for example, we can measure CSF SOD1 levels to make sure we're silencing or reducing the expression of SOD1, and we can also look at plasma neurofilament as a way of assessing whether or not we're decreasing the degeneration of spinal motor neurons and brain motor neurons. So I think it's important to realize that one of the key criteria we used in selecting these programs is that we can efficiently de-risk, if you will, and gain proof of biology and proof of concept.

Great. And then just a follow-up. I know that the SOD1 ALS program has an asset currently under regulatory review from Biogen. Can you discuss the results you've seen from that asset so far and the level of confidence it gives you as you progress toward the clinic with your asset, as well as how it might influence the treatment landscape in the future?

Well, everything I've seen is based on public information. From what I see, if we use baseline neurofilament as a covariant presented at the recent NCA meeting, that there is efficacy on several important clinical outcome measures, including the functional rating scale. I think there are certainly reports of patients who have had very long extensions of survival, which I think is pretty remarkable. So, I look forward to seeing more data, particularly as the file. I guess they've now filed for approval and the PDUFA date, I believe, is next January. I expect to see much more data. By the time we get into the clinic, we'll see a lot more data from the FDA briefing documents and other documents in the public domain. So, we'll learn a lot from that and leverage whatever information we get and incorporate it into our clinical development plan.

Next question comes from Divya Rao with Cowen & Company.

This is Divya on for Phil. Congrats on the quarter and the exciting pipeline update. Just, two questions from us. One, based on Voyager's previous clinical data, especially in Parkinson's disease, do you see any overlap in the current pipeline programs? Obviously, other than in terms of the actual candidate that you're selecting that would potentially enable rapid entry and progression through the clinic. And then just a more, I guess, specific question, the limitations with AAV, especially when delivered systemically, is the increased liver accumulation. I was wondering if you had any comments on what you're seeing in terms of liver accumulation with these capsids either in rodents or the nonhuman primates.

Thanks, Divya. Those are great questions. First of all, in terms of overlap, the previous Parkinson's program, which was actually terminated last year, and it was a partnership with Neurocrine, was a different payload. It was actually delivering AADC aromatic l-amino acid decarboxylase and it was using intraparenchymal—convection-enhanced intraparenchymal delivery. Our program is very different. We plan to go with IV-delivered TRACER capsids. So different capsid, different route of administration, different payloads. Here, we're going to— the payload is GCase, the enzyme that is encoded by GBA. Ours is more of a disease-modifying approach. I would say there's not too much overlap with the program that was terminated. I don't know if Todd has anything to add before I jump to the next part of the question on liver.

No, I think you captured it. I think importantly, the goal of doing something that could be disease-modifying is the key.

And then in terms of the liver, that's a great question. One of the reasons why we're excited about the TRACER capsid is that not only do they increase tropism into the desired organs like the CNS, but many of them show at the same time, detargeting organs like the liver where we see toxicity. So that's very promising. The second thing is that since they're so potent at getting into the brain with IV delivery, we hope to be able to use lower doses. In fact, we're going to show data in the dose range finding studies that we can achieve lower doses, which should also help with the liver toxicity issues.

Yes. So Al, you captured it. It is a great question. I think the whole field has seen toxicities in the DRGs and in the liver. What we're seeing with our capsid, as Al pointed out, is we identify those capsids that deliver into the brain while detargeting the liver and dorsal root ganglion and potentially other regions as well. It's one of the things that we are finding most telling about the TRACER capsids, in addition to that enhanced BBB penetration that would allow a lower dose.

The next question comes from Yun Zhong with BTIG.

So the first one on the technology platform. Do you have a sense of your expectation of the dose level that you will achieve to establish sufficient exposure in the brain? And sorry, have you looked at immunogenicity? Because often, when dealing with novel capsids, we have seen a lot of unwanted immune responses.

I'm going to start to answer these questions. Thanks for the great question.

Excellent questions. Thank you. With the dose levels, what we're seeing— we reported this at the ASGCT therapy conferences that we are able to achieve substantially better delivery. So 100-plus-fold better delivery into the brain versus the current state-of-the-art AAV9. We're anticipating some additional reports on this upcoming key therapy conferences. As for immunogenicity, by and large, we're making modifications specific to these capsids. We're targeting particular loops that we've identified that we can modify without causing problems with the capsid. By and large, those do not impact the immunogenicity that we've seen. So, preexisting immunity so far is very similar to the parental capsid. We have not identified any increased immunogenicity up to now.

Okay. So if I can ask a follow-up question about indication, I know with your experience with Alzheimer's and with the company's experience with Parkinson's is reasonable. But given the complexity of the pathophysiology behind those diseases, what's your comfort level that you will be able to use a gene therapy approach to target those very complicated neurodegenerative diseases?

Yes. Well, let me start, and Todd could also answer. I believe that by targeting the — we chose targets that are highly validated. In the case of PD, for example, we're going to start with the subset of patients that have GBA mutations. It's a pretty large subset, as we estimate up to 10%. Some papers say 5%, some say 10%, but up to 10% of Parkinson's patients have a GBA1 mutation, the most common genetic risk factor. I think it is a complex disease. But I think by targeting that very large subset of patients who are GBA carriers, we reduce the complexity. We also can measure whether or not we’ve replaced the enzyme, another de-risking maneuver that we can do early in clinical development. We can see whether or not we've replaced the enzyme and gotten to normal expression or at least getting toward normal expression of the enzyme by looking at cerebrospinal levels. In terms of Alzheimer's disease, again, I think tau is a well-validated target. The progression of tau correlates better with dementia than any other biomarker, and the ability to image tau and measure phosphorylated tau or pathologic forms of tau in the CSF and blood greatly help us de-risk the program. So I'm very optimistic not only about our ability to do therapeutics in these diseases, but I think the whole field has learned a lot, and we're going after well-validated targets using modern measurement tools. So I'm actually very optimistic.

This concludes our question-and-answer session and Voyager Therapeutics' second quarter 2022 conference call. Thank you for attending today's presentation. You may now disconnect.