Voyager Therapeutics, Inc.

Good morning and welcome to Voyager Therapeutics first quarter 2023 conference call. All participants on a listen-only mode. There will be a question and answer session at the end of this call. Please be advised that this call is being recorded at the company's request. A replay of today's call will be available on the investor section of the company's website approximately two hours after completion of this call. I would now like to turn the call over to Pete Frong Chu, Chief Financial Officer. Please go ahead.

Thank you, and good morning. Joining me on the call today are Drs. Al Sandrock, CEO, and Dr. Todd Carter, our Chief Scientific Officer. We issued our Q1 2023 financial results press release this morning. The press release and 10Q are available on our website. We plan to provide a brief summary of key highlights from the quarter and reserve the majority of time for Q&A. In a moment, I will turn the call over to Al. Before I do this, I want to remind everyone that during this call, Voyager representatives may make forward-looking statements, as noted in slide two of today's deck. These forward-looking statements include future expectations, plans, and prospects. All forward-looking statements are inherently uncertain and are subject to risks and uncertainties that may cause actual results to differ materially from those indicated by these forward-looking statements. You are encouraged to review and understand the various material risks and uncertainties facing the company as described in the company's most recent annual report on Form 10-K filed with the SEC. As of the filing of today's quarterly report on Form 10-Q, there have been no material changes to the risk factors described in our annual report. All SEC filings are available on the company's website. Now, it is my pleasure to turn the call over to Alex.

Thank you, Pete, and good morning, everyone. Please turn to slide three. I'd like to take a moment to recognize the incredible innovation happening right now in neurotherapeutics and in gene therapy. We believe we are witnessing a renaissance in neurotherapeutics. Just this year, the second disease-modifying therapy for Alzheimer's disease received accelerated approval, and the first drug was approved for Friedreich's ataxia. We've seen breakthroughs in treating negative symptoms of schizophrenia, something for which there are no approved therapies. Just two weeks ago, the FDA granted accelerated approval to an antisense oligonucleotide for SOD1 amyotrophic lateral sclerosis. Importantly, the FDA based the approval on the finding that treatment-driven reductions in neurofilament are reasonably likely to predict clinical benefit in SOD1 ALS patients. establishing a precedent for a biomarker-based path to accelerated approval. I hope this will drive further new treatments for patients suffering from this devastating disease. At the same time, the gene therapy field is coming of age. We have recently seen the FDA approval of the first gene therapy for hemophilia B. Gene therapies offering important potential advances in treating Duchenne's muscular dystrophy and hemophilia A are approaching sedupa dates. And through that, we may see the accelerated approval path utilized for a gene therapy. Importantly, long-term data on Zolgensma, one of the first gene therapies approved, recently demonstrated durability of effect after 7.5 years, which physicians have called transformational. Voyager sits at the intersection of neurotherapeutics and gene therapy, and we believe we are uniquely positioned to leverage the advancements in both fields. To date, the delivery of gene therapies into the central nervous system has proven challenging. Approaches to inject these therapies into the brain parenchyma or various CSF spaces have not been very successful. Voyager's tracer capsid discovery platform is the foundation of our approach to solving this delivery challenge. Voyager scientists have engineered multiple capsid libraries, each with more than 20 million novel variants of AAV9 and AAV5 capsids to select those novel capsids that display greatly increased transduction in the central nervous system following intravenous delivery. We have leveraged these capsids to advance our own and our partners' CNS gene therapy programs, several of which are now advancing towards clinical trials. This is how Voyager is enabling the future of neurogenetic medicine, and from where I sit, it's an incredibly exciting place to be. Moving to slide four, I will briefly review our investment rationale. Our first pillar of value is our tracer capsule discovery platform, which I just discussed. In the preclinical study, our novel capsids delivered intravenously have demonstrated more than 100-fold higher transgene expression in the brain compared to conventional AAV9 capsids. We have shown high levels of CNS gene expression at low doses, and we have demonstrated the ability to target specific cells such as neurons or glia while detargeting the liver and dorsal root ganglion cells. We look forward to sharing more data on our capsids at ASGCT later this month. Our second pillar of value is our CNS pipeline. We are advancing four programs through late research and towards IMD. Two of these programs are wholly owned, our humanized anti-Tau antibody for Alzheimer's disease and SOD1 gene therapy program for ALS. The other two, our GBA-1 gene therapy program for Parkinson's disease, and our frataxin gene therapy program for free dry phataxia, are being co-developed with NeuroPrint. Our third pillar of value is partnerships. We completed TAPS at option and license agreements with Pfizer and Novartis. We've executed strategic collaborations around our pipeline programs with NeuroPrint. and we are exploring more such transactions. Turning to slide five, we continue to make progress advancing our CNS pipeline. I'll note a few recent highlights. During the first quarter, we selected a lead humanized anti-Tau antibody candidate, VY-Tau01, for the treatment of Alzheimer's disease. In March, we presented new data at the ADPD meeting highlighting the differentiating characteristics of this lead candidate. Last month, we received pre-IND written feedback from the FDA for BY-PAL01. Borger continues to expect to initiate GLP toxicology studies this year to enable an IND filing in the first half of 2024. Another change this quarter was to the timeline for our SOV1 ALS gene therapy program. Voyager previously said we expected to identify a lead development candidate for this program in the first half of this year. That has moved out to the second half of this year as we continue to evaluate data from this program to identify the optimal development candidate. We intend to provide updated guidance on the IND timeline once we select the development candidate Given where we are today, we expect the IMD to occur in mid-2025. Our frataxin gene therapy program for plebryx ataxia and our GBA1 gene therapy program for Parkinson's disease and other GBA1-mediated diseases both continue to advance in collaboration with Nurocrine. I'm pleased with the progress we're making here. Additionally, during the first quarter, We launched two new early-stage gene therapy programs combining vectorized siRNAs with our novel intravenous tracer capsids. One combines two siRNAs to enable specific knockdown of mutant HCT and MSH3 for the treatment of Huntington's disease. The other uses siRNA to reduce tau expression in the brain for the treatment of Alzheimer's disease. I'd like to now turn the call over to Pete Moinshew to discuss our financial results for the quarter.

Thanks, Al. I will cover some key financial points on this call and refer you to our press release and 10Q issued today for further details. Please turn to slide six. We announced Q1 2023 collaboration revenue of 150.5 million, composed of 69.5 million from the 2023 Nurocrine Collaboration Agreement for the GBA1 program, $79 million from the Novartis option exercises, and $2 million from the 2019 Nurocrine Collaboration Agreement activities. Our R&D expense was $18.6 million, an increase of $4.2 million as compared to Q1 2022. driven by increased headcount, increased program-related R&D spend, and milestone fees, and offset by decreased facility costs. Our G&A expenses were $9 million for the first quarter of 2023, as compared to $7.7 million for the same period in 2022. The increase in G&A expenses was primarily a result of increased compensation costs driven by headcount increases. As a result of strong revenues in Q1 2023, the company had net income of 124 million, resulting largely from our collaboration revenues, as well as increase of 1.8 million in other income due primarily to increased interest revenue from cash and marketable securities. Regarding the balance sheet, Voyager reported $273.3 million in cash, cash equivalents, and marketable securities at the close of March 31st, 2023. We also had a receivable at the close of Q1 2023 from Novartis's $25 million option payment received in April. Together, this resulted in pro forma cash, cash equivalents, and marketable securities totaling $298.3 million for the close of the quarter. Of note, deferred revenue increased by $18.7 million, related primarily to the upfront payments from Nurocrime allocated to the three new discovery programs of $74.4 million, offset by the recognition of $54 million into revenue from the Novartis options exercise. The company has a sound balance sheet enabled by our non-diluted collaboration revenues. We expect that our balance sheet plus expected reimbursements will be sufficient to meet our planned operating expenses and capital expenditures into 2025. I will now turn the call back over to Al. Thank you, Pete.

Turning to slide seven, as you can see, Voyager has had a productive start to 2023. We began the year by securing $175 million upfront payment in strategic collaboration with Neuroclim Biosciences, followed by Novartis' opt-in decision on capsids to two neurologic disease targets, triggering another $25 million payment. These transactions strengthened our balance sheet and enabled us to further advance our platform and pipeline. As discussed, we selected a development candidate for our anti-cal antibody program for Alzheimer's disease. We aimed to select a development candidate for the ALS SOD1 program later this year, and we launched two new early-stage gene therapy programs for Huntington's disease and Alzheimer's disease. In addition, I'm thrilled to welcome George Skangos, to our board of directors, as we announced in a press release this morning. George is one of the most accomplished executives in the entire biotech industry, having served as CEO of Beer, Biogen, and Exelixis. His vast experience building biotech companies that deliver highly innovative therapies to patients while creating value for shareholders will be invaluable to us as we strive to develop Voyager into a leader in neurogenetic medicine. Looking forward, we continue our work to break through the barriers constraining the fields of gene therapy and neurology. We will continue to share the exciting data we are generating at scientific conferences, including at ASGCT later this month. Importantly, our pipeline advancement is leading towards what we view as multiple opportunities for value creation. As we look towards 2024 and 2025, We anticipate the potential for multiple IMD filings across our wholly owned and collaborative and or licensed programs. This translates into multiple opportunities to earn milestone payments, and even more importantly, as clinical trials begin, several shots on goal to establish human proof of concept for our novel capsids. Furthermore, there is potential to see early biomarker-based evidence of disease impact in some of these very difficult CMS indications. And of course, we continue to engage in active discussions with potential partners around our platform and pipeline. In summary, it's been a great start to 2023. And as always, it is all due to the incredible Voyager team. I look forward to continuing our momentum throughout the year. With that, we're happy to take any questions you may have.

Thank you. If you would like to ask a question, please press star 11 on your telephone. And as well, wait for your name to be announced before you actually ask your question. One moment while we prepare our Q&A roster. The first question that I have today will be coming from Jay Olson of Oppenheimer. Your line is open.

Oh, hey, congrats on all the progress, and thank you for taking our questions. We're interested in the work you're doing on tau. You're advancing an anti-tau antibody and initiating a tau knockdown gene therapy program and could potentially have a vectorized anti-tau antibody. Can you just talk about how you'll optimize the development strategy and prioritize all of your different tau targeting modalities? And then eventually, do you think that anti-Tau therapies can be monotherapies, or do you think they are best to be combined with anti-A-based therapies? And then finally, can you just talk about how you'll balance the tradeoff of advancing your Tau therapies independently versus seeking a partner? Thank you.

Thanks, Jay. Those are great questions. So, first of all, what we like about tau is that we believe it's a very important and well-validated target for Alzheimer's disease. And because of that, we're taking multiple approaches against this target. And so, as you pointed out, we have an antibody against the C-terminal domain of tau. The development strategy there is to move forward with the the passive antibody first and see whether or not we get proof of concept. In other words, to see whether or not we can block the spread of tau by looking at tau PET scan. We think this is very feasible, and we can do it with not that many patients over a one-year period. If we obtain proof of concept, then we have a couple of choices there. One is we can continue to proceed with the antibody to tau. all the way through to approval, and or we can then initiate a vectorized anti-tau activated program. So, that would be the sort of the crossroads that we will see there. In addition, we have this vectorized tau knockdown, which we think is an additional shot against a very important target. And this will be different in the sense that it doesn't rely on antibodies binding to extracellular TAL. This approach is to decrease the expression of all forms of TAL, intracellular and extracellular. And we saw some preliminary evidence of that approach at the ADPD meeting with the Biogen-Ionis antisense against TAL, where they were able to see effects on TAL PET imaging. So, we think it's a very important target. We think having multiple approaches is helpful against this target. And we think we can obtain proof of concept pretty rapidly in the clinic, taking advantage of Caltech imaging. The final question relates to whether or not we're going to partner. And, you know, we're always talking to partners, and we're always open to anything. We could go to proof of concept by ourselves. We have the capability to do that, and I believe we have the resources to do that. However, you know, we're open to anything. But ultimately, I can't imagine that we could go all the way to commercialization for a disease as large as Alzheimer's disease. So, we will need to partner that program. The question is when, and we have some choices there. Finally, your question about combination or a monotherapy. I believe, look, I think we just started the era of disease-modifying therapies for Alzheimer's disease with the approval, accelerated approval, of two anti-A-beta antibodies. As we all know, the efficacy is modest in the 25% to 30% range on the CDR from a BOS. We'd love to get better treatment effects. And one approach might be to combine with a tau-reducing approach, whether it's an antibody or a knockdown. And so, I think that we're going to, you know, we are likely to test combination treatments. Because I think once tau spreading starts to occur, you may need to address tau independently separate from the amyloid antibodies or in combination with them. I hope that answers all your questions, Jay.

That was perfect. Thank you so much for taking on the questions.

Thank you. One moment while we prepare for the next question. And our next question will be coming from Jack Allen. Again, please wait for your name to be called before you ask the question. Your line is open. Jack Allen, your line is open.

Oh, sorry about that. I was on mute. Thank you so much for taking the questions, and congratulations on all the progress. I wanted to stick with the TAL theme here as well, and I wanted to ask Al, I'm sure you're aware of the Eli Lilly results from their recent study where they measured TAL and stratified patients by TAL. I was wondering if you had any early thoughts on a specific population within the Alzheimer's disease group that you looked in role and Any comments you have around the differential effects it seems like Eli Lilly saw in their higher versus intermediate cow cohorts?

Hi, Jack. That's a really interesting question. I look forward to seeing the data at a scientific conference. But from what I gather, the people who had the higher cow burden when they started the treatment had less of a treatment effect. And I think that underscores, I think, what I was just saying that we may need combined with a TAL approach, a TAL targeted therapy. And so, in terms of the population, you know, even when we get enrolled patients with mild cognitive impairment, which is the earliest symptomatic disease, the disease is pretty far advanced in terms of molecular pathophysiology, right? I mean, not only has amyloid been accumulating for up to 20 years and have reached essentially a maximum burden in the brain, we see tau has already started to progress in many of these patients. And so, I think that even when you do the combination, you're going to need to go to an early stage of patient, at least MCI, and maybe even earlier.

Got it. Great. Thank you so much for that insight. And then I was also wondering if you had any comments on the competitive landscape that relates to TAO and any other programs you're closely monitoring to see early proof of concept in this space?

Well, I think that, you know, there are a number of mid-domain targeted antibodies that are now approaching readouts from efficacy trials, to my understanding. So, that'll be very interesting. You know, in our hands, We had multiple mid-domain antibodies that we could have humanized ourselves. In our hands, they weren't as consistently effective in the spreading assay in the animal studies where we take human pathological tau, inject them into the animals, and look at the spread of pathological tau. So, we're very hopeful that our C-tomo antibody remains differentiated, but I think it'd be wonderful to see efficacy with the mid-domain antibodies, these Alzheimer's Do these patients need something additional, I believe, in addition to the anti-amyloid therapies? Todd?

I just wanted to add that from our studies, at least in our preclinical model, it's pretty clear that the epitope matters quite a bit. So there are mid-dominant antibodies of our own that work, and there are mid-dominant antibodies that don't work, our C-terminal antibody. as Al mentioned, gave us the most robust and strongest effects. So, I think that as we see these antibodies come through the clinic, it will be very informative for the whole field to learn, hopefully, what works and then maybe what doesn't.

Great. Thank you so much for the call, and congratulations again on the progress. Thanks, Chad.

Thank you. One moment while we prepare for the next question, and our next question will be coming Phil Naidoo of TD Cowan. Phil Naidoo of TD Cowan, your line is open.

Thanks for taking our questions and let us out our congratulations on progress. A couple from us, keeping on the TAO theme. In terms of the TAO antibody that you've chosen as the development candidate, how does that antibody compare to the one that produced the data at AAIC 2022? Is it simply a humanized version of that prior antibody or are there any other changes?

Go ahead, Todd. Sure. It's the – so we have shown data on a number of antibodies. The data you're talking about from AHIC included data from multiple panels of antibodies with different epitopes. The antibody we're taking forward is a humanized version of the lead antibody from that presentation.

So it's a humanized version of the antibody that produced the 71% to 74% declines in Yes. Yeah, okay. And then second, on the GLP-TOX, it sounds like you're going to complete the GLP-TOX and be able to file an IND within a year. That strikes us as faster than average. How can you get that done so quickly? Is that based on feedback from the FDA or just prior experience?

It's both, actually. And, you know, there have been other immunized antibodies against pathologic The tricky part here is that the target for the antibody is not expressed in wild-type animals, which is typically what's used in tox species, as the tox species, right? So, in order to look at on-target toxicity, you have to look in animal models, where that's the only place that you have the pathological pal as being expressed. Those models, you know, the animals don't do well. They die prematurely because of the disease. And so you have to work within the limitations of that. But so we do have experience with humanized antibodies against pathological proteins in the brain. And so we've drawn on that experience. But also we have FDA feedback. And so our preclinical toxicology plan is based on both.

Great. And then one last housekeeping question for Peter. Peter, the $25 million milestone that was received in April, is that all going to be booked in Q2, or is there going to be an amortized component?

We, from a REVREG perspective, recorded that obviously in Q1, but cash is in Q2. Perfect. You can see that in the numbers. Got it. Thank you.

Thank you. One moment while we prepare for the next question. And our next question will be coming from . I'm sorry, of Wells Fargo. Your line is open.

Hi. Thanks for taking our questions. Perhaps a TAO question and a SOD1 ALS question. So for TAO, how would you think about the criteria for success once you get the TAO antibody PET imaging data? given the findings of the tau antisense, as you mentioned before. I'm guessing mainly if tau reduction on PET is less potent, then if there's still a reason that the antibody approach can be a reasonable modality to be further pursued. On SAAT-1, the question is, could you give more color on the delay for the nomination of the candidate? Is it more about payload or vector optimization or some other reasons? Thank you.

Thanks. Those are great questions. I'll take the first one, and Todd will take the second one. On the TAO, you know, well, first of all, the anti-sense oligonucleotide is injected into fecals. And so in our antibodies is an intravenous drug that we're gonna inject every four weeks. So that's a pretty big difference right there in the mode of administration. We will obviously compare to others that are showing data on tau. We do have a minimum product profile that takes into account our competition. And so we will move it forward. If we have, first of all, we have to have And then we'll compare to competitors and see if there's space for an additional treatment. Just keeping in mind the different modes of administration, the higher ease of use of an intravenous antibody, and the fact that, you know, I think there's room for more than one treatment. When I was a physician, I always liked having multiple options for my patients. Todd?

So on side one, as you know and pointed out, the development candidate in therapy is a combination of a capsid and a payload, the transgene. We're continuing to work and evaluate the transgenes in our capsids. Our capsids continue to perform very well. I invite anybody on the call to check out the ASGCT presentations next week. We have a symposium presentation, an oral presentation, and some posters on our novel capsids. We're seeing quite reproducible results and continued performance across the blood-brain barrier. What we're trying to do is identify the optimal payload with the optimal capsid to meet our candidate criteria. We hope to do that in the back half of this year.

Got it. Thanks for taking the questions.

Thank you. One moment while we prepare for the next question. And our next question will be coming from Laura Chico of Wedbush. Your line is open.

Good morning. Thanks very much for taking the question. I guess, Al, staying on the TAL team, I wanted to ask if with the upcoming reimbursement decision for the anti-amyloid antibodies, is there any learnings there that can inform or perhaps change your development strategy for TAL? And then one for Pete. Can you just remind us, it's obviously been a big year in terms of milestones coming in, the potential for any remaining milestone payments in 2023? Thanks, guys.

Thanks, Laura. Yeah, on the reimbursement question, that's a really important question, and we have a lot to learn, I think, as the year goes on this year. But I think, look, we have to be mindful of the total number of patients that are going to require treatment, and we don't want to do anything that'll be, you know, unhelpful to society. We want to help patients, and we want to make sure patients have access to the drugs. And so, I think there's a lot for all of us to learn in the coming years. And so, but I think you're pointing to the concept that if there's a combination treatment, that's two drugs that have to be reimbursed. And so, we'll have to take that into account.

Yeah, Laura, with regards to your second question, so we don't provide a lot of forward-looking guidance with regards to future milestones. I know we've shared publicly the milestones relative to all of our partnerships and relationships that we have in aggregate and kind of with some right now, but a lot of that's been redacted. I can say it this way. With regards to our existing relationships, there are some more of a near term, I would say it that way. But again, we don't guide specifically with regards to those. And so, you know, I think that's most probably where we would leave it for now. Hopefully that helps.

Thank you very much.

Yeah, thank you very much, guys.

Thank you. One more while we prepare for the next question. And our next question will be coming from June Lee of Threat Security. June Lee, your line is open.

Hey, thanks for taking our questions. You know, for the Huntington's program, it's interesting that you're taking both an allele-specific and non-allele-specific approaches with SNP and MSH targeting. Can you elaborate a little bit on your strategy here? And do you plan to include multiple siRNAs in a single construct to address multiple SNPs? And would you also combine SNP as well as MSH in a single construct? Thank you.

Yeah, thanks. I'll start and I'll ask Todd to finish the answer. So, I would say that in some ways, both are kind of an allele-specific, both targets, because MSH3 targets the expansion, which only occurs off the mutant. And obviously, the allele-specific mutant Huntington targets is an allele-specific approach. So, in some ways, I look on it as both are kind of preserving, both targets, by targeting both of these, we're preserving the expression of wild-type Huntington, which I think is the goal. Because, you know, I think there's a lot of concern that we need to preserve wild-type Huntington expression. So, and then, yeah, I mean, I'll let Todd answer, but our aim is to combine both Si vectorized Si RNAs into the same vector. Go ahead, Todd.

Yeah. So, that's right, Al. So, we do plan doing and incorporating both siRNAs. The payload for the siRNAs is relatively small. So, it's not a problem to fit multiple in a single vector. We can do a bisistronic approach. Now, that said, I mean, we could explore and evaluate these independently as well. So, that's always an option we could choose to move forward with. We plan on going after MSH3 PAM. the pan matter, which would affect the mutant alleles specifically, and then the approach to the allele-specific Huntington is a SNP-based approach to knock that down in an allele-specific manner.

So, Jude, you're right that, you know, a SNP-based approach, we're not going to be able to treat every single Huntington patient. We'll start with the most common alleles. And then ultimately, we may need to do a second allele-specific MH, you know, mutant HTT program and so forth. But, yeah. Okay.

Go ahead. Thank you. Thank you. I have a follow-up on the TAL program. You know, you have, as someone, people alluded to, you have multiple programs, multiple shots on go. You have the approach to targeting intracellular species as well as the intracellular species with the sRNA. Is there one species in your view that is probably more important to address? Or I know you probably say both, but which one has more like evidence as a more dangerous or pathogenic form?

Well, I wish I knew the answer to that question. I think that's part of the complexity here is that there are multiple forms, if you will, of how in the extracellular space. And, you know, it's pretty certain that targeting just the enterminal containing extracellular species of cow probably doesn't work because the multiple approaches have to try it for those. But I think that I don't have an answer. Maybe, Todd, do you know what the pathologic species is?

No, I don't. Yes.

No, I mean, so, you know, more along the line. Yeah, more along the lines of, you know, intracellular versus extracellular, because your mRNA approach would target, I believe, the intracellular species preferentially.

Yeah. Well, it actually will target both. I mean, it'll target the synthesis of all forms of tau. So, if we decrease, we will definitely increase intracellular, which the antibody probably won't be able to do very much at all. But it will also target extracellular tau, too, because that the source of extracellular tau is intracellular tau.

Would you say that the SRNA approach then would have a little bit higher probably a success or that's still TBD?

Well, yeah, but, you know, every approach is going to have its own benefit-risk profile and mode of administration issues and things. I think it's still too early to know to be certain which approach is going to be optimal for patients. But I think it's such an important target. We wanted to go after it with multiple approaches. Thank you.

Thank you. One moment while we prepare for the next question. And our next question will be coming from Sumit Kalp. your line is open.

Thanks for taking my question. Nice to see all the progress as the company has worked here in exciting times to be targeting the specific conditions that you are. So, I have a question on your SOD1 ALS gene therapy program. Now that Topazin is available, how do you expect the landscape to change with respect to clinical trial recruitment? And is there any merit in running a specific preclinical model in combination with Topazin?

Okay, I think I heard the first question, but I'll start, and then I'm not sure I heard the second one, but I think the first question relates to the feasibility of recruiting patients in the setting of a person being approved. And I think there's, first of all, it's wonderful that patients with a terrible disease have treatment options. So, congratulations to Biogen and Ionis for getting that across the finish line. For us, you know, we could either take patients who are already on to the person and give them the gene therapy and see if the requirements for the person is decreased, perhaps to zero, but it could just be decreased. And we can track neurofilament as a marker to know whether or not the treatment is adequate, for example. Another approach would be to go to untreated patients There may be parts of the world where it's hard to access the person. And so, and then a third approach would be to go very early, even before symptoms, to get rid of the toxic gain-of-function autosomal dominant mutation. So, those are the three approaches we're considering now, and time will tell whether, which one of these is the best option. But I think it's, I think that the, as I alluded to in my, comments, the fact that neurofilament is considered by regulators, at least FDA, as a validated surrogate outcome measure only helps in terms of making the development more feasible, I believe. And you may have to repeat the second question because I'm not sure I heard it.

The second part of that was, is there any merit in running a specific preclinical model for your gene therapy in combination with toficin to optimize the product?

So, the question was whether we're doing preclinical studies. So, there are a couple of SOD1 transgenic mouse models, G93A, G37R, et cetera. We could add, do the combination study. in vivo, but I'm not certain that that would be necessary before we did the study in patients. I think that we have a very good blood-based biomarker that we can use to monitor patients in terms of the amount of injury to motor neurons. And some of these animal models, they're not very predictive of what happens in the clinic. So, I worry about relying too much on these animal models.

Got it. Thank you.

Thank you. Again, if you would like to ask a question, please press star 11 on your telephone. The next question is coming from Jack Allen of .

Great. Thank you so much for taking the follow-up. I just wanted to reach out and see if you have any comments around the ability of nonhuman primates. I know earlier this year there was a ban of importation of these critical research assets, and I wanted to gauge your, I guess, awareness of this and any comments you have as it relates to your preclinical programs that you have ongoing.

Hi, Jack. It's Todd. So, that's a great question. I think the entire field is watching very carefully. We certainly are watching the non-human primate availability quite closely. To date, we have not been adversely affected by non-human primate availability. We set up agreements with multiple vendors to make sure we have options in case an issue should arise. And all I can say is that we're doing our best to mitigate any risk Watching very closely.

Good. Thank you so much.

Thank you. This concludes today's Q&A session. There are no more questions in the queue. I would like to call, turn the call back over to Dr. Al Sandrock for closing remarks.

Thank you, everyone, for joining us today and for the great questions. Feel free to follow up with us directly if you have any further questions. Thanks again.

Thank you, everyone, for joining today's conference call. This concludes today's event. You may all disconnect. And, everyone, have a great rest of your day.