Good day, and welcome to the Selecta Biosciences phase I SEL-399 top-line data conference call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded. I'd now like to turn the conference over to Kevin Tan. Please go ahead. Thank you and good morning. During this call, we will discuss the top-line data report from the phase I clinical trial of SEL-399 empty capsid in healthy volunteers. The press release reporting the results in today's presentation are available in the Investors and Media section of our website, www.selectabio.com. A copy of this presentation will be available with the current report on Form 8-K, which was filed this morning with the Securities and Exchange Commission, or SEC. Joining me today are Dr. Carsten Brunn, our President and Chief Executive Officer, Dr. Peter G. Traber, our Chief Medical Officer, and Dr. Kei Kishimoto, our Chief Scientific Officer. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, development, efficacy, and regulatory and clinical prospects of our product candidates, including SEL-399, future expectations, plans, partnerships, and prospects. These statements are subject to various risks, including those related to the COVID-19 outbreak that are described in our filings made with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements which speak only as of today, November 8th, 2021, and Selecta disclaims any obligation to update such statements even if management's views change. I would like to note webcast participants can view the slides alongside the call. I would now like to turn the call over to Dr. Carsten Brunn. Carsten? Thank you, Kevin, and good morning. I appreciate you joining us today, and I'm really excited to be sharing the top-line results from the phase I clinical trial of SEL-399 empty capsid in healthy volunteers, which we conducted jointly with AskBio. I want to specifically acknowledge Dr. Jude Samulski, AskBio's Chief Scientific Officer and Co-Founder, for his invaluable contributions. Dr. Samulski is also assisting with the development of Selecta's gene therapy programs as special advisor. Moving to slide three. Adeno-associated virus or AAV vectors are the most widely used in vivo gene therapy vectors. However, because AAV is non-self-replicating, transient expression may wane over time, particularly in growing tissues such as the liver in childhood. This suggests that redosing of gene therapy may be necessary. However, gene therapy with AAV induces a robust immune response in recipients, resulting in high level anti-AAV neutralizing antibodies, or NAbs, which precludes redosing of gene therapy. Because NAbs can reduce the efficiency of gene therapy, treatment with AAV gene therapy is restricted to patients with low levels of pre-existing NAbs. For example, Zolgensma, an FDA-approved gene therapy product for SMA, requires NAbs titers to be less than or equal to 1:50 to be eligible for treatment. In addition to induction of anti-AAV NAbs, the immune response to AAV gene therapy may involve in gene therapy associated toxicities such as hepatotoxicity and thrombotic microangiopathy. Therefore, the ability to inhibit development of AAV-specific antibodies has the potential to be transformational for the field by enabling redosing of AAV gene therapy. In the human proof of concept study presented today, we studied the ability of ImmTOR, which induces immune tolerance to coated antigens to inhibit the development of NAbs to AAV8 in healthy volunteers. The AAV vector used in the study is an AAV8 empty capsid particle, which has an intact viral particle but lacks encapsidated DNA and therefore will not express a transgene and has no therapeutic effect. Moving to slide four. The immune system reacts to AAV8 by activating antigen-presenting cells, such as dendritic cells, which ultimately leads to production of anti-AAV antibodies by plasma cells, which prevent redosing. In addition, activated dendritic cells and cytotoxic T cells can lead to cellular damage, and in the case of the liver, result in liver inflammation and loss of efficacy. Moving to slide 5. ImmTOR has been observed to have multiple effects on the immune response to AAV in animal studies. The uptake of ImmTOR particles by dendritic cells induces tolerance through the production of antigen-specific T regulatory cells or T-regs, which can inhibit activation of effector cytotoxic T cells. T-regs also inhibit antibody production by B cells and thereby prevents T cell-dependent anti-AAV antibody production. Additionally, the inhibition of dendritic cell and cytotoxic cell activation may prevent liver inflammation. Finally, ImmTOR has been observed to induce autophagy in hepatocytes. In less technical terms, ImmTOR may lead to enhanced and more durable efficacy and improved safety. In the human study presented today, we're focused on the potential ability of ImmTOR to inhibit the formation of anti-AAV antibodies. With that, I now transition the call over to Peter to review preclinical data and discuss top-line data from the first in-human empty capsid study. Peter? Thank you, Carsten, and good morning to everyone joining the call. If you could please move to slide 6. The human study data that we present today builds on animal data where we observed ImmTOR preventing the formation of anti-AAV antibodies. In mice treated with an empty capsid vector, the same AAV preparation used in our human study to be presented, the empty capsid was observed to induce a robust antibody response beginning as early as seven days following administration, increasing to a peak by 12 days and with sustained levels thereafter. A single dose of ImmTOR inhibited the antibody response in all mice out to day 27, with an increase in antibody formation at day 42 and thereafter in three of the six mice. However, when three monthly doses of ImmTOR were administered, antibody formation was inhibited in all six animals through day 168, the last data point in the experiment. This demonstrates the potential of a single dose of ImmTOR to delay the immune response against AAV8, which can be sustained long term with two subsequent ImmTOR doses. Formation of anti-AAV8 antibodies was also observed in non-human primates treated with an AAV8 gene vector that contains a transgene called SEAP, although the response was somewhat delayed in comparison to mice. Like what was observed in mice, some animals that received a single dose of ImmTOR had antibody formation at later time points. Three monthly doses of ImmTOR maintained minimal antibody formation through the end of the experiment at day 84. These data indicate that if anti-AAV8 antibodies can be inhibited through day 30 in the human study, we can potentially maintain inhibition by administering two monthly doses of ImmTOR. For the human study presented today, a single dose of ImmTOR was employed. Therefore, based on our learnings from the animal studies, the focus of the presented results is on day 30 following the administration of AAV8 empty capsid. Please move to slide 8. The study had two general objectives. The first was to determine the immune response to AAV8 empty capsid in healthy volunteers. To our knowledge, this is the first time an AAV empty capsid without a DNA payload has been administered to humans to help clarify the contribution of the AAV capsid to the human immune response. The second objective was to determine whether immediate pretreatment with single escalating doses of ImmTOR can reduce the immune response to AAV8 empty capsid. This will help clarify our dose regimen moving forward. The primary endpoints that will be presented today are anti-AAV8 NABs and adverse events. Multiple additional immunologic measures are under evaluation as secondary and exploratory endpoints, and we intend to present the results of these evaluations with our partner, AskBio, in future scientific presentations and publications. However, the NAB responses reported today represent the most important data for the study objectives. Please move to slide nine. A total of 23 volunteers were enrolled, 14 males and nine females. All subjects had an anti-AAV8 NAB titer of less than one - five at baseline. Subjects were randomized, the treatment with ImmTOR was placebo-controlled, and the study was double-blinded. The study was designed as a single intravenous dose of ImmTOR, followed immediately by a single intravenous dose of AAV8 empty capsid, with follow-up over 90 days, during which multiple measurements of NAbs and safety labs were evaluated. All three groups studied received empty capsid in a dose of 2 × 10^12 viral particles per kilogram body weight. In group one, three subjects received an infusion of saline as a placebo for ImmTOR, followed immediately by empty capsid. In group two, three subjects received an infusion of saline, followed by empty capsid. Nine subjects received an infusion of 0.15 mg / kg of ImmTOR, followed by empty capsid. In group three, two subjects received an infusion of saline, followed by empty capsid, and six subjects received an infusion of 0.3 mg / kg of ImmTOR, followed by empty capsid. Please move to slide 11. The data demonstrated that a single dose of ImmTOR inhibited formation of NAbs at day 30 following treatment, which was the key time point as determined from animal studies. Shown on a linear scale, empty capsid alone induced high-level NAbs in the majority of subjects. Treatment with ImmTOR resulted in markedly reduced NAbs formation in the majority of subjects receiving 0.15 mg / kg of ImmTOR, and in all the subjects receiving 0.3 mg / kg of ImmTOR. Through expansion of the scale using a log transformation of the data to better differentiate between low values, we observed that a single dose of ImmTOR of 0.3 mg per kg reduced formation of NAbs to less than or equal to a titer of 1 to 25 in 100% of subjects, and to less than or equal to a titer of 1 to 5 in 67% of subjects. Please move to the next slide, 12. This is a plot of the median levels of log transformed values for NAbs titers over time from day zero to day 30. Administration of empty capsid alone resulted in a strong antibody response by day seven after administration and reached a peak by day 14. In contrast, the formation of NAbs was markedly reduced during the entire 30-day period with ImmTOR treatment. By day 30, there was a 250-fold lower median level of NAbs in subjects administered 0.3 mg per kg of ImmTOR versus administration of empty capsid without ImmTOR. Additionally, we observed a dose-response relationship between the two doses of ImmTOR. Slide 13, please. After day 30, there was a progressive rise in median NAbs titer in the ImmTOR-treated groups, eventually ending in similar levels to empty capsid alone by day 90. The individual levels of NAbs at 90 days shows that two of the six subjects in the 0.3 mg per kg ImmTOR group had titers of less than or equal to 1:25, with one of them having a titer less than or equal to 1:5. Slide 14. Both the 90-day human and non-human primate NAb data are reproduced on this slide so that a direct comparison can be made. There is similarity in the distribution of NAb titers at day 90 between humans and non-human primates following a single dose of ImmTOR. However, when three monthly doses of ImmTOR were administered to the non-human primates after a single dose of empty capsid, there was complete inhibition of NAbs. This is encouraging for a potential long-term effect of three doses of ImmTOR in humans. One way to conceptualize neutralizing antibodies with respect to redosing of gene therapy is also shown on this slide. A target of NAbs for gene therapy dosing can be considered up to a titer of 1-50. While there is a range of values in gene therapy trials, a titer of 1-50 is used for therapy eligibility criteria of the marketed drug Zolgensma, a successful systemic gene therapy for spinal muscular atrophy. It is noted that redosing in this range may be dependent on the dose of AAV gene therapy for the given indication. In the intermediate range, antibody levels may interfere with efficient redosing and therefore ancillary approaches such as pretreatment with IgG protease to reduce antibodies may be required for redosing. High levels of antibodies are not compatible with redosing. Next slide 15. From a safety perspective, all treatment-related adverse events were expected for ImmTOR, readily monitored and transient. We did not observe any serious adverse events. There were no unexpected AEs based on evaluation of 280 subjects treated with ImmTOR in other clinical trials. The most common AE was mild to moderate stomatitis, observed in 3 of 9 subjects in the 0.15 mg per kg ImmTOR group, and 6 of 6 subjects in the 0.3 mg per kg group. Stomatitis onset was on average 11 days after drug infusion and lasted for an average of 8 days. The symptoms of stomatitis were ameliorated with steroid mouthwash treatment. The next most common AE was mild to moderate rash, which was observed in 3 of 9 subjects in the 0.15 mg per kg ImmTOR group and 3 of 6 subjects in the 0.3 mg per kg group. The average day of rash observation was day 12, and the rash resolved after an average of 23 days. No therapy was required for any rash. Regarding laboratory alterations, three asymptomatic laboratory AEs were seen in subjects receiving ImmTOR. Two subjects had mild to moderate thrombocytopenia, with onset at nine days after infusion and recovery after an average of 23 days. One subject had a transient asymptomatic Grade three elevation in serum triglycerides observed nine days after infusion. Now I'll turn the call back over to Dr. Carsten Brunn. Carsten? Thank you, Peter. This is really very promising data. Please go to slide 17, and let me summarize. We were able to demonstrate for the first time in a clinical study that AAV8 anticapsid elicited a strong immune response in humans. The peak median anti-AAV8 NAb titer was 1:6,875 at day 14 after infusion, which was maintained at high levels through day 90. The addition of a single dose of ImmTOR to administration of empty capsid inhibited the formation of anti-AAV8 NAbs in a dose-dependent manner at day 30. At the 0.3 mg per kg dose of ImmTOR, 100% of subjects had a NAb titer less than or equal to 1:25, and 67% had a NAb titer of less than or equal to 1:5. At day 30, we observed median NAbs titers of 1-5, a 250-fold lower NAbs level when compared to subjects dosed with AAV capsid alone. After day 30, ImmTOR-treated subjects showed delayed formation of NAbs, reaching control levels by day 90. However, 2 of 6 subjects treated with 0.3 mg per kg ImmTOR maintained NAbs titers less than or equal to 1-25. Based on prior animal studies, we believe that if NAbs are inhibited at day 30, administration of two additional monthly doses of ImmTOR has the potential to maintain control of NAbs beyond day 90. Safety findings included AEs previously observed with ImmTOR. We believe this promising study in healthy volunteers provides support for the potential use of ImmTOR for the mitigation of NAbs to AAV in gene therapy clinical trials. We look forward to presenting further details from the study characterizing the immune response of healthy subjects to anti-capsid in a peer-reviewed scientific manuscript and at a major gene therapy conference jointly with AskBio in the future. In conclusion, this pioneering human proof-of-concept study demonstrated for the first time that AAV8 anti-capsid elicited a robust immune response in humans. We also showed for the first time that ImmTOR, in combination with the widely used AAV8 capsid, has the potential to overcome the significant challenge of the formation of anti-AAV8 NAbs. Reduction of capsid immunity could be transformational for the field of gene therapy by making gene therapy safer and possibly enabling repeat dosing. We're looking forward to seeing ImmTOR's potential benefits advancing to the clinic. On this remark, I'm closing the presentation and will open the call up for questions. Operator? Thank you. We'll now begin the question-and-answer session. To ask a question, you may press star then one on your touch-tone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we'll pause momentarily to assemble our roster. Our first question comes from Kristen Kluska from Cantor Fitzgerald. Please go ahead. Hi. Good morning, everybody. Thanks for taking my questions and congratulations on these results. First, given safety has been viewed as a concern in the space from high-dose AAV administration, which has been seen both in non-human primates and patients, how have you thought about specifically how much of the dose you may allow to scale back on in light of both, one, the potential to redose and, two, the potential added first dose benefit in ImmTOR, which was established in preclinical data? I guess in a nutshell, I'm asking how will you choose doses to try to stay as safe as possible but still want to see an effect with ImmTOR? Yeah, Kristen, that's a great question. Obviously, as you know, in this study, we did not have a transgene, so we're only specifically able to look at NAb titers, which as you saw were significantly reduced. You're right, and what we observed in the non-human primate study where we saw 60% higher expression of the transgene, there is the potential to give lower doses of ImmTOR, which will result in a better safety profile. Obviously, ultimately, I think one of the really transformational approaches would be instead of giving patients one high dose, which you especially see in the neuromuscular disorders, you give potentially multiple lower doses to avoid some of the safety issues seen in those studies with high titers. Okay, thanks. You have a number of partnerships and collaborations, including some that are specifically related for gene therapy applications. Could you reiterate for us the main drivers these companies had and their level of comfort in working with you even ahead of seeing this first clinical data readout? Now that you have this data on hand, how do you expect this could help both those ongoing partnerships and collaborations as well as other conversations you may be having? Yeah, that's a great question as well. Obviously we do have a number of exciting partnerships already prior to this data, you know, simply based on the animal studies, the partnership we have with AskBio, with Sarepta and Takeda. Obviously everyone is looking specifically to potentially improve the efficacy of gene therapy, but also the ability to redose. I think today's data release is an important first step to indicate that, you know, ImmTOR is able to inhibit the formation of neutralizing antibodies in a meaningful way. Obviously there's more questions to be answered specifically around the first dose benefit, but I think today was an important step and I think further confirms the animal data that led those companies to enter into a collaboration with us. Okay, thanks. While I recognize the issue of neutralizing antibody formation is not unique to just AAV8, do you have any thoughts as to how the effect could look when looking at other capsids? Yeah, that's a great question as well. Obviously we picked here AAV8 as it's a widely used vector in the clinic. We have replicated the data with various different vectors. I think we looked at AAV8, AAV5, AAV3 and AAVrh10. So we believe we're agnostic to the serotype, and we have demonstrated this in a number of animal studies. Okay, great. Congrats again. Thank you, Kristen. The next question comes from Raju Prasad from William Blair. Please go ahead. Thanks for taking the question. You know, given this data set, obviously, you know, you're looking towards maybe using multiple doses. Can you just give us a sense of how you're thinking about those studies moving forward? Would you think about taking the 0.15 dose forward in multiple dose studies, given the additive effect you see in animal models and in gout? Just curious to know your thoughts there on kind of long-term benefit. Yeah. I think we would definitely go into the clinic with three monthly doses. I think you know, this study has confirmed that we're able to inhibit the formation of NAbs at day 30. We know from the non-human primate study if we give three monthly doses, we can maintain control. I think we would start with three monthly doses. We haven't guided exactly on the doses of ImmTOR, but obviously we're very pleased here to see a clear dose response with the 0.15 and the 0.3. You know, there's good rationale to potentially start with 0.5 and then 0.15 and then increase over time in a dose escalation way. Great. Can you just remind me, is there data that you have pre-clinically or some confidence you have that, you know, following three doses that we won't see, you know, we'll see a kind of continued decline in neutralizing antibodies and that won't pop back up? Yeah, that's a question we get a lot. You saw in one of the earlier slides on slide 6, actually, we showed data from a mouse study where we had a longer follow-up out to day 168. That's obviously, I think, almost a quarter of a lifespan for a mouse. I think that's a pretty good indicator that you know we're able to extend. Obviously the thinking is that you know after 3 months you no longer have the capsid around that induces the immune response. I think that's the other important consideration as well as we have shown in animal studies that ImmTOR actually extends the half-life of the capsid. We think by day 90, the capsid is no longer around. Great. Maybe just one last one. I saw kind of at the bottom of the press release on the MMA update. Is this, you know, do you consider the MMA to be probably the first time we're gonna see ImmTOR usage in a clinical trial? Or do you think that there's a chance that some of the partnership programs that you've already struck might kind of move to the clinic, you know, in a faster way and show data there? I'm just kind of curious as to when we might see, you know. Yeah. The next important data set. That's a great question. Obviously, MMA is our first wholly owned program where we plan to take ImmTOR into the clinic with an AAV capsid. It's hard to comment on the other partnerships, you know, as we don't have control over timing. We basically outlicense ImmTOR to our partners. We're focused on MMA, and we think that's the first one to be in the clinic in a gene therapy setting. Great. Congrats on the data. Thank you. Thank you, Raju. The next question comes from John Newman from Canaccord. Please go ahead. Hi, guys. Thanks for my question and congrats on the data and also the execution here, given COVID. Just had two questions. The first one is: Given the potential design of the MMA study, do you think you might actually have a little bit of an advantage in terms of your enrollment versus other gene therapy studies given if ImmTOR is working as we expect it to, if a patient goes into that study that maybe they're more comfortable that they will derive benefit? The second question I had is: How do you think you might explore some of the other technologies that you've recently licensed, like the IgG proteases? Would you look mainly to use that technology to broaden the pool of eligible patients going forward? Thanks. Yeah, a great question. Maybe I'll let Peter address the first question around the potential benefit in MMA and why you know, especially the parents of those kids might be highly motivated to have the kids enrolled in this study. Peter? Yeah. Thank you, John. I think, of course, the parents of children with MMA scrutinize clinical trials to enroll their children in very carefully. The biggest issue is that if you are enrolled in an AAV gene therapy trial, you just get one shot at it. You can't get redosing. That's a very important consideration for families. While we would project that there's a potential to redose in a trial with ImmTOR, that very well may be an issue that the parents take into consideration. I think your observation there is correct. It may have a competitive advantage. I would also mention that we're doing the clinical trial at the NIH Clinical Center with Dr. Charles P. Venditt i, who's a key expert in MMA, and they have the largest following of MMA patients, so therefore, they'll be able to focus on the patients. I think that gives us an advantage for recruitment of this trial as well. Thanks, Peter. In regards to your second question, around the IgG protease that we in-licensed called Xork, you're right, John. We see it as positioned to address patients with pre-existing immunity. We know that up to 40% of patients have been exposed to a natural AAVrh10 infection and are not eligible to gene therapy, and we believe you know, this is a compelling solution here. We have demonstrated you know, Xork is from a non-human pathogen, has very low cross-reactivity actually to human sera. So I think we're in a unique position here to have a protease that can address I would say, the second you know, large unmet need around expanding the potential patient pool eligible for therapy. Okay, great. Thank you. The next question comes from Gil Blum, from Needham & Company. Please go ahead. Good morning, everyone, and let me also add my congratulations. Because this has kind of been addressed a little bit before, the 2 to the power of 12 dose isn't the level of dosing we usually see for things like, you know, BMD and other systemic therapies. Do you guys think that because of the, you know, nature of potential increased expression at lower doses, you can actually play around in this range? Yeah, that's a good question. Obviously, we used this dose in the non-human primate study, so we wanted to have comparable results and obviously it's a healthy volunteer study, so I think we also had to be mindful around the dose. We have used higher doses in animal studies, and I think in the presentation, we go up to 2 × 10^13 in the mouse data and still saw very good control with ImmTOR. You're right. I mean, one of the potential benefits could be that you are able to give multiple lower doses actually instead of hitting patients with a single high dose. Even so, you know, we haven't tested this yet, but that's definitely a consideration as well. I'm happy to have Kei or Peter add some additional color. The only thing that I would add, this is Peter, is to say, even based on the results that we have here, you could redose the gene therapy at day 30. So we, you know, we want to suppress antibodies much longer with multiple doses of ImmTOR, but even in this study here, we reduced NAB titers at day 30 to a level where you could redose. That strategy that Carsten described of giving two lower doses of gene therapy could be done on the basis of the results we showed today. Yeah. That makes sense. Maybe I have a bit of a different question. Just k ind of to remind us, so on administration of AAV vectors in general, do you expect to usually see, you know, ALT and other liver enzyme elevations? Is that something that generally happens and maybe didn't happen in this study? Or is that related to, you know, other factors in the gene therapy space? I'll let Peter answer that question. Yeah, that's a very good question. You know, in gene therapy trials with increasing doses of AAV therapy, you do see increased transaminase. Potentially that leads to liver inflammation, which can reduce the expression of the transgene. That does appear to be a dose-related effect. In those trials that have you know, 1e14 or greater, see quite a bit of that. You still see an increase in transaminase at lower doses, like in the hemophilia trials. It doesn't occur in all subjects, and it's not clear whether it's a combination of the capsid and the transgene that might be part of that. We saw some minor elevations, but we didn't see a consistent pattern to suggest that the empty capsid alone at these doses induced hepatotoxicity. Okay. That also makes sense. Maybe a last one, and I know you kinda touched upon this in your previous answers. Could you potentially hypothesize on the mechanism by which antibodies stay as long as they? You know, formation of antibody happens as late as it does. Okay. It kind of suggests that the AAVs remain in circulation. I think you guys mentioned something similar earlier. Yeah, I'll let Kei Kishimoto answer that. Yeah, we have some data that shows that, you know, ImmTOR extends the half-life. But, Kei Kishimoto, I'll let you address this question. Yeah. In one of our earlier monkey studies, we showed that when you combine ImmTOR with AAV, you can get significant extension of circulating AAV levels. I mean, it's not high levels, but obviously it's sufficient to induce still an immune response. Okay. Again, allow me to add my congratulations and, we'll hope to see a lot more from, you know, gene therapy clinical studies of redosing. Thank you, Gil. The next question comes from Yun Zhong, from BTIG. Please go ahead. Hi. Thanks very much for taking the question. I believe you have done some redosing studies in animals, and I wondered, do you think you have seen a material difference when you combine the second dose with ImmTOR or without ImmTOR? For human patients, do you think you will eventually need to run a redosing study, or just by showing the lack of neutralizing antibody will be sufficient to support potential use in redosing? I have a follow-up question, please. Yeah. Good. I'll let Kei answer the first question around redosing animals, whether we use a ImmTOR with a second dose. Kei? Yeah. Absolutely. I think because with gene therapy you're not giving it like other drugs that need to be dosed more chronically. I think we would always give the ImmTOR together with any dose of AAV vector. Thanks, Kei. I think around the redosing, Yun, I think, you know, we believe, you know. This is pure speculation at this point. For example, for MMA, we would of course initially look at efficacy with a single dose of AAV capsid, and we'll look at prevention of neutralizing antibodies. We believe this will probably be enough for regulatory approval. I don't think we would have to show the actual redosing. This could be kind of a post-approval commitment. This is a speculation at this point. Okay. Looking at the neutralizing antibody production, looks like some patient who got the 0.3 mg per kg, their neutralizing antibody level at day 90 is actually higher than those empty capsid-treated patients. Is there anything that suggests there could be anything mechanistically behind this higher than just a capsid alone production? Yeah. We don't believe so, and obviously there's you know biological variation in the response. You're referring to one outlier with a very high titer. Right. 600,000. If you kind of take that out, the median titers are very comparable. Actually, if you take that number out, you're also at about 1,000. Actually, I'll let Kei make the reference that a lot of people obviously is top of mind with COVID. You know, people respond differently to COVID. Maybe, Kei, you wanna make that point. Sure. I mean, the immune system is very heterogeneous from individual to individual, so there's a lot of genetics associated with MHC, the T cell repertoire, the B cell repertoire. It's not unusual for, you know, people to have very different immune responses to the same challenge. The COVID example is, you know, obviously some people may have asymptomatic symptoms to COVID infections, while on the other extreme, you can get very serious life-threatening infections. What we don't know for that one subject that got the high titer at day 90, we don't know obviously what that subject's titer would have been if it hadn't gotten ImmTOR. Great. Thank you. Great. The next question comes from Ram Selvaraju from H.C. Wainwright. Please go ahead. Hi, this is Boobalan dialing in for Ram Selvaraju. Thanks for taking my question. Firstly, what could be the possible reasons for the observed delay in response in non-human primates versus mice? Good question. I'll let Kei Kishimoto to answer that. I mean, there could be a number of factors. You know, obviously, primates aren't mice. You know, one difference in those graphs is that the mice, as Carsten put it, pointed out, got a dose of 2 x 10^13 particles per kilogram. Whereas the monkeys, the dose was 2 x 10^12. Thank you. What are some of AskBio's initial thoughts on the study results? You obviously saw the quote from Jude Samulski. Obviously one of the first findings of the study is for the first time, we're actually able to show that empty capsid elicit a strong immune response. I think that's a first in humans. Obviously very encouraged by the ability to inhibit NAbs with a single dose of ImmTOR. I think we're aligned here that this is an important step to enable redosing. Okay. One final question from me. What regulatory requirements may need to be fulfilled if the plan is to get ImmTOR approved as a standalone therapy for a combination with a broad range of gene therapy approaches, rather than getting specific combinations of ImmTOR and particular gene therapies approved one at a time? Yeah, that's a good question, and I'll start maybe and I'll let Peter comment as well. Obviously, we always need, at least initially, some tox studies looking at specifically a specific disease model. So we think, you know, initially we'll get approval for single indications, maybe down the line, once there's more evidence, we might get broader approval for certain, you know, disease categories or vectors. I think initially we would think it is gonna be specific to a disease model. Peter? Yes, I agree with that, Carsten. I really don't have anything to add there. The disease specificity is really gonna be important for the first number of approvals. After that, we may be able to generalize, as Carsten said. Thanks for taking my questions. Again, congrats. Thank you, Boobalan. This concludes our question and answer session. I'd like to turn the conference back over to Carsten Brunn for any closing remarks. Yeah, thank you, operator, and thank you to everyone who joined us this morning. Stay safe and healthy, and this concludes today's call. Thank you very much. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.