Good morning, and thank you for joining us today for Volume 10 of our Investor and Analyst Event Series. We are excited to share with you today a first look at patient data from our EXPLORE44 trial. But before we get started, I will be sharing an excerpt of our forward-looking statement. This presentation contains forward-looking statements as defined under applicable law. Forward-looking statements involve risks and uncertainties, both known and unknown, which may cause actual results to differ from the forward-looking statements contained in this presentation. You are cautioned not to place undue reliance on these forward-looking statements and to refer to the more detailed cautionary language in this slide and in the risk factors section of our recent reports filed with the SEC. And now, I would like to hand over to our President and CEO, Sarah Boyce. Thank you, Mike. Good morning, everybody. I'm delighted that you've joined us for this morning's webcast. Our vision at Avidity is to profoundly improve people's lives by revolutionizing the delivery of RNA therapeutics. The data with del-zota that we're going to share with you this morning is a further example of how we're delivering on that vision. You can go to the next slide, please. So the purpose of the update today, we're gonna be presenting you the initial data from the Phase I/II EXPLORE44 study. This is data from the 5 mg cohort, given every six weeks, and this is data from the 4-month time point in the study. You'll see five things: unsurpassed delivery to muscle, robust exon skipping, statistically difference, difference in dystrophin production, and also the exon skipping, a profound reduction in creatine kinase, along with a favorable safety and tolerability profile that we'll also share. In terms of what's next for del-zota, we're looking forward to regulatory interactions and understanding on how we can carve the most expeditious path to accelerated approval. We'll also talk about what this means for our global DMD franchise beyond DMD 44, and the fact that that is now all moving full steam ahead. Now, looking towards the data, and I'm gonna show you sort of highlights of what we're gonna talk about today, and then we'll get into it more. First and foremost, what we're seeing is unsurpassed delivery to muscle. We are delivering more PMO to muscle cells than anyone has ever done before. That's about 200 nM. That's about 3x-5x what any other delivery technology has been able to achieve. We know for DMD and with exon skippers and with PMOs, it's really all about delivery. When you get that delivery, then you see results like we've seen. Significant exon skipping, a 37% increase in exon skipping, and up to a 66% increase in exon skipping, measured by digital droplet PCR. We also then, in turn, see a significant increase in dystrophin production, and that's a substantial increase of 25% of normal in dystrophin production. So I'll refer to you to the graphic that's also on this slide, and it's a 25%. That's the delta. So baseline was 7%, 25% increase, taking people to 32%. And actually, the restoration was up to a total of 54% normal. A 32%, that takes us clearly well into Becker's range, which is considered to be over 10, and starting to move closer and closer to more and more production of that normal dystrophin protein. With that, then also what we see is a profound reduction in the creatine kinase biomarker. Creatine kinase is very elevated in people living with DMD. It is a key marker of muscle damage, and what we're seeing is these levels reduced to near normal, with a greater than 80% reduction when compared to baseline. And we'll also share with you the favorable safety and tolerability profile. So let's get into it. Joining me today are my colleagues, Steve Hughes, Mike Flanagan, and Mike MacLean, who introduced us. We will now move into... I'm now gonna hand over to Steve, who will take you through aspects of design, safety, next steps. Mike will take us through the data, and then we'll come back for a Q&A at the end, which will be facilitated by Mike MacLean. With that, I'm gonna hand over to Steve. Thanks, Sarah. So if we can go to the first slide. Duchenne muscular dystrophy, or DMD, is a severe disease with reduced or absent dystrophin, causing progressive muscle weakness and disability, loss of ability to walk by the early teens, and a significantly reduced life expectancy. Overall, there are about 10,000-15,000 people living with Duchenne in the USA, with a similar number in Europe. It's an X-linked disorder, so it primarily affects males. Del-zota is for DMD44, our drug, AOC 1044 d el-zota is specifically designed to skip exon 44 in order to restore dystrophin production, and there are about 900 patients in the USA and a similar number in Europe, with DMD amenable to exon skipping of exon 44 or DMD44. Today, we'll be presenting data from the 5 mg/kg cohort of the EXPLORE 44, Phase I/II clinical trial in people living with DMD44. So I'd just like to spend a few moments reminding you of the high-level design of this study. So EXPLORE44 is a Phase I/II study. It's actually our first in-human study for this drug. It's a multiple dose study. It's also a dose escalation study, so we're testing multiple doses at 5 mg/kg. The data we're sharing today is the lowest dose in the patients. Targeted enrollment is 24 participants, and we have a broad age range from 7- 27, which means that we've involved both ambulatory and non-ambulatory patients. All patients in all cohorts have biopsies. The muscle biopsies are from the biceps muscle, and they're open biopsies. All participants are, on completion of EXPLORE44, able to roll over into an open label extension study. As this is a first in human study, the primary objectives focus on safety and tolerability. Secondaries look at PK, PD, exon skipping and dystrophin levels, and then the functional endpoints, patient-reported outcomes, and the quality of life are all exploratory endpoints. If we could go to the next slide. Treatment groups are generally well-balanced on the baseline characteristics, but I'd like you to cast your eyes down to the second row from the bottom. You'll notice that both groups have very high creatine kinase levels, and as Sarah mentioned, this is a characteristic of Duchenne muscular dystrophy and is caused by the extensive muscle damage that's going on. Next slide. As with our other programs, del-zota has shown favorable safety and tolerability. There were no related AEs occurring in more than one patient. There was one serious AE leading to discontinuation. This was a case of true anaphylaxis that occurred at the mg/kg dose level. The patient experienced a transient fall in blood pressure during the infusion. This resolved rapidly on discontinuation of the infusion and administration of epinephrine, and the patient actually was able to go home just a few hours later without requiring hospitalization. FDA was informed and didn't place any restrictions on the study. We were able to continue dosing the 5 mg cohort and dose escalate to the mg/kg dose. this is the only time we've seen this in any of our programs, including at the high dose of 10 mg/kg in this program. There was also one other event that resulted in stopping the study drug. This was a classical infusion-related reaction that was moderate in severity. This also occurred at the lowest dose of 5 mg/kg, and we've not seen any similar reactions at mg/kg dose. just as a reminder, we're not using any pre-medication routinely across any of our programs. Importantly, there have been no symptomatic hemoglobin changes, no hypomagnesemia, and no renal events. As Sarah alluded to earlier, the data we'll be showing you in just a moment is truly remarkable, once again demonstrating the power and consistency of our AOC platform. These remarkable data and yet another rare neuromuscular disease provide an imperative for us to bring del-zota to DMD44 patients as rapidly as possible. In this slide, I'm going to walk you through the changes we're making to the EXPLORE44 program in order to achieve this goal. Firstly, we've determined that we do not need to dose escalate mg/kg. this study originally had three patient cohorts, with a cohort B3 at 20 mg/kg. we've removed 20 mg/kg cohort. the dystrophin levels that we're seeing mg/kg are well within the Becker's range, and we know that we don't need to go above 10. This means that enrollment is now complete for the randomized, placebo-controlled EXPLORE44 study. Patients from the EXPLORE44 study roll over into the open label extension study, EXPLORE44- OLE, and we'll actually be amending this open label extension study to enroll an additional 10-15 new patients in order to gain more experience at both doses. Completion of enrollment of the EXPLORE44 study allows us to move up our regulatory interactions, and accordingly, we've now initiated interactions with FDA to discuss the fastest route to an accelerated approval, and we're moving as quickly as possible to secure regulatory alignment. I'm now going to pass you over to Mike, who will share the data from the study. Thanks, Steve, and good morning, everyone. Thanks for joining. We're really excited about sharing the data today, and what I'd really like you to focus on once again is the robustness and consistency of our data. From unsurpassed delivery, PMO delivery to muscle, to a 37% increase in exon skipping, to significant 25% increase of newly produced dystrophin compared to baseline and restored total dystrophin to as high as 54% of normal. This dramatic increase in dystrophin results in profound decrease in creatine kinase to near normal levels, suggesting the improved health of muscle tissue. So once again, we've connected the dots. Unsurpassed delivery of muscle, robust exon skipping, meaningful production of dystrophin, leading to profound decrease in creatine kinase biomarker. Now, the one differentiating feature, differentiating feature of exon skipping technology and of d el-zota is that it produces near full-length dystrophin. In the top panel is full-length dystrophin. In the middle panel is a representative del-zota-produced, nearly full-length dystrophin, and on the bottom is an example of gene therapy-encoded micro dystrophin. We believe that the near full-length dystrophin retains many of its biological activities and may lead to better muscle function. So the first step in producing this near full-length dystrophin is delivering PMOs to the muscle, and that's shown on the next slide. So what we, what we've seen is unsurpassed PMO delivery to muscle at one month following three doses of del-zota at 5 mg/kg. Just to orient you to the graph, the y-axis shows concentration of PMO in the muscle, the x-axis shows the different dose groups, healthy volunteers in the dark, and DMD44 participants in blue. Following a single dose of del-zota at 5 mg/kg, we measured 40 nM of PMO in muscle biopsies in healthy volunteers. This was one month after dosing. We presented these data last December, and at that time, this was unsurpassed delivery of PMOs to muscle. And now, in DMD participants, following three doses of del-zota, we observed 200 nM mean levels of PMO in the muscle. These data really highlight the robust delivery afforded by our AOC technology, featuring our anti-transferrin receptor monoclonal antibody that we use across all our programs. It's with this unsurpassed PMO delivery that we really were interested in seeing what the effects of exon skipping. Here we show statistical significance of 37% increase in exon 44 skipping compared to baseline following treatment with del-zota, with skipping as high as 66%. On the y-axis, shows exon skipping, and on the x-axis are the placebo group or the del-zota-treated participants at baseline and 4 months. Not surprising, the placebo cohort in gray, shown on the left, show no change in exon skipping between baseline and 4 months later. In contrast, in the far right bar, you can see DMD exon 44 participants treated with del-zota saw a mean exon skipping of 44% and a change from baseline biopsies of 37%. These were statistically significant changes in exon skipping. Now, these participant biopsies were collected from the bicep and analyzed using digital droplet PCR for exon skipping. Part of that biopsy was also used for immunoblotting or Western blot for dystrophin production, and that's shown next. Here we show a statistically significant increase of 20%-25% of normal in dystrophin production compared to baseline, following treatment with del-zota, with total dystrophin production as high as 54, 54% of normal. On the y-axis is the dystrophin levels, as shown as% normal dystrophin. On the x-axis are the placebo group and the del-zota-treated participants at baseline and 4 months. Again, the placebo group is shown in gray, and we saw no changes in dystrophin during the 4 months. While participants treated with del-zota, as shown in the blue bars, saw a mean total dystrophin production of 32% and a significant increase by 25% of normal of newly produced dystrophin compared to baseline. So what does this mean? We've tried to provide a figure on the far right that helps illustrate the change in dystrophin observed after del-zota treatment. Now, this, the range of normal dystrophin is calculated as 0%-100%. Generally, people living with less than 10% dystrophin are diagnosed as having Duchenne muscular dystrophy. As you can see, our average baseline was 7% in this, this population, and following del-zota treatment, we saw a significant mean total dystrophin of 32%, which is starting to approach healthy levels of dystrophin. The absolute change is a significant increase of 25% normal levels of dystrophin. With this significant increase in nearly full-length dystrophin, we are interested to see how it would translate to improvements in muscle health, as measured by creatine kinase. As shown here, we see a dramatic decrease of 80% in creatine kinase levels that approach near normal, near normal levels. On the y-axis is creatine kinase levels, on the x-axis are the study days, and the arrows indicate dosing of either placebo or del-zota. Shown in gray are the mean values of the placebo group, and shown in blue are the mean values of the del-zota group. The dotted line denotes the upper limit of normal for creatine kinase. As you can see in the placebo group, the creatine kinase levels hover around 7,000 units of enzyme. In the del-zota group, shown in blue, following the first dose, we observed a marked drop in creatine kinase that continues to fall to near normal levels one month after the third dose. These significant changes in creatine kinase strongly suggest that del-zota treatment is improving muscle health. With these positive data, next slide. With these positive data, we're now focused and committed to pushing forward additional exon-skipping AOCs to advance our growing DMD portfolio. So this morning, once again, we've connected the dots from unsurpassed delivery to muscle, to a significant increase in exon skipping, leading to an increase in dystrophin that's resulted in a profound decrease in creatine kinase biomarker, suggesting an improvement in muscle health. And with that, I'll pass it back to Sarah. Thank you, Mike. As Mike said, we are now committed to full steam ahead with our DMD franchise. We're also deeply aware of the partnership with the DMD community that will be needed to advance treatment options, and that's both patients themselves, their families, patient advocacy organizations, and all of the people at the clinical trial sites who brought us to where we are today with this data. I would also like to make sure that we thank all of the sites involved in EXPLORE44, but most importantly, the families who are participating in the study and the boys and the young men who are part of the study. As a reminder, FDA has granted orphan drug status, Fast Track, and Rare Pediatric Designations to del-zota, and EMA has also granted Orphan Drug Designation. Enrollment in EXPLORE44 is complete, and as Steve also talked to, we plan to enroll an additional 10-15 patients in the EXPLORE44 open label extension study. Part of our next steps is also looking forward to regulatory interactions to discuss about what is the most expeditious path to accelerated approval. When we have updates around that, we will provide them. If we can go to the next slide, please. I'll just close, reminding on our vision, which is to profoundly improve people's lives by revolutionizing the delivery of RNA therapeutics. I hope what you've seen today is another example of the work we're doing and the data that we're seeing that is bringing us further and further towards that vision. I'll now ask my colleagues to join me, and we'll move into Q&A. Okay, so we have lots of questions coming through. The first question comes from Cantor, Eric Schmidt and Josh Schimmer. First of all, they congratulate us on the unprecedented data. There's two, two parts to this question. I'll split it, split this up. The first is: Is there anything about exon 44 that would make it more or less difficult to achieve high levels of full-length dystrophin expression? Mike, do you want to start on that one? Yeah, I can take that, that question. Yeah, it's a, it's an interesting question because it has a, a number of different layers, so I really appreciate it as a, as a good first question. So when we, when we looked at the landscape, we really felt, you know, of course, we want to go where there's no therapeutic, and really high unmet medical need, which I think is clear for, DMD or Duchenne muscular dystrophy and exon 44. So we started there, and we were, we were told by a number of luminaries in the field and others that, "Don't do exon 44," like, "It is gonna be too hard. There's background, expression of dystrophin. You're not gonna be able to see any increase above that. You know, that has some intrinsic skipping." But we really felt that it was just such a high unmet medical need and very few people are working in this space, and we thought that our AOC technology could really have an impact here. So we kept plugging along and kept moving forward with non-human primate data, selecting sequences. We had very interesting mouse data that we've shared before that really showed that we could have an impact on skipping and dystrophin production, and it's really what has led us today to show that unsurpassed delivery. I think that's really the key thing with our technology. And once you have that delivery, everything else falls into place. You get the skipping. The skipping obviously results in dystrophin production, and these are levels that really others have not seen. So the early advice to avoid exon 44, while we appreciate advice. You know, sometimes we just don't follow it, and we just push forward. So, you know, I don't think there's anything easy about, about Duchenne muscular dystrophy. People have been working on it for decades, and I think finally we're starting to see progress, meaningful progress, that we hope will really, transform people's lives, both the boys and young men, as well as their families. So, you know, we're focused and committed to pushing the whole portfolio forward, not just exon 44, but everything, and as go as fast as we can because we know people are waiting. Thanks, Mike. The second question, I think, Steve, you could probably start to give the answer here. Can you remind us of the data packages, number of patients, follow-up biomarkers, that led to other approvals in the exon skipping field? That's also a multi-layered question. It's a few PMOs that have been approved in this field, and the range of patients involved for those individual programs does vary a little bit, from not far removed from the number of participants that we have on the EXPLORE44 program up to the earlier approvals had more patients, in the range of 76 to 100, if my memory serves me right. The other thing is that regulatory expectations around the number of participants involved, at least to satisfy things like safety database requirements, does vary according to the size of the patient population that you're serving. And for some of the other exons, such as exon 51, those have larger patient populations than the exon 44 skippers. So this is really an ultra-orphan indication, and so we would anticipate that the regulatory expectation may well not be as high as for some of the other exons in terms of total safety database. Okay, thank you. Our next couple of questions come from Ritu Baral at Cowen. Steve, I'm going to stick with you here for a minute. The first question is, what functional endpoints of data do you plan to show eventually from this data set? So we do have a number of functional endpoints. Let's remember that the study is enrolling both ambulatory and non-ambulatory patients. So we have included the North Star Ambulatory Assessment, but we won't be able to do that in every one. We've also included the PUL Upper Limb Assessment. We're assessing other measures of muscle strength and then a number of patient-reported outcomes focusing on various and different parameters, including quality of life. Okay, and then, Ritu, second question for you, Mike. When could we see the first 10 mg data, and would you expect to see dose response on exposure, skipping and dystrophin levels? Yeah. So as Steve indicated, we've fully enrolled the 10 mg/kg data, and we're just waiting for those data to come through. We're gonna look at the totality of the data, both at 5, as you saw already, that looks remarkable, and at 10 mg/kg, and then we'll decide what makes the most sense for people living with DMD44 and look at the total increase in dystrophin. I think based on our previous studies, based on some non-human primate data as well as our mouse model, it may be difficult to get much higher than what we have, but of course, we're going to complete the clinical study, the phase I/II EXPLORE44, and look at the data and then make that decision. Yeah, so it's, you know, it's the first—it's our first program. I wish I could give you a great answer, but it's our first program in this space, and we're just gonna have to see as it comes along, and that'll help set us up to move faster for the other programs. Yeah. I mean, I would just add, you know, as always, we'll make data-driven decisions. As we've said, the study is fully enrolled, and it is still ongoing. So, you know, people are still receiving placebo in the study as well. When we get the data, we'll make a data-driven decision. And we're really... I think, just to echo Mike's point, we're carving, you know, a whole new space here, essentially with the type of data that we have. So we'll review the data and make a data-driven decision. With regards to enrollment of the additional participants into the open label extension study, our plan is to enroll both at five and 10. Thank you, Mike and Sarah. Now, the next question is, or set of questions, I should say, are from Joe Schwartz at Leerink. First, you know, making a hockey reference in the summertime, he says, "Congratulations on achieving a hat trick with all three clinical programs." So thank you for that, Joe. Some of these questions I think have been asked and answered, so I'll move it to the question on CK reductions. He sees them as very impressive. Are you evaluating time function tests and/or NSAA in these patients? If so, when might that data be reported? Steve, do you want to start with this one? Yes, so we are evaluating the North Star. We are evaluating other measures of ambulation as well. We haven't given guidance on when we're going to report on the functional endpoints in the study. Obviously, it's very remarkable to see changes in creatine kinase and particularly near normalization of that from very high levels that really hasn't been seen before, at least not with sustained reduction over time. So that gives us great confidence that we're affecting the biology of the disease in a very positive way. It's just a little early right now to be expecting changes in the clinical endpoints. I would say we've seen some encouraging trends, just nothing that's quite mature enough at the moment to share. Okay. Sticking with you, Steve, what is your strategy to execute clinical development in an environment where gene therapy is available? So, talking about to the market as a whole or to patients as a whole, gene therapy really isn't for everyone. There are contraindications to gene therapy around patients that have pre-existing antibodies to the virus vectors. Patients... Not all patients choose to have gene therapy, and then gene therapy doesn't work for everybody. So there's definitely a patient pool out there that will be available to us for further clinical development. And actually, with these data, these data are so remarkable that that could really change, certainly within the DMD44 community, people's perception or desire to have gene therapy, as opposed to enrolling in our clinical trial with a PMO. Okay, last question from Joe, and I'm sticking with you, Steve. How much have you investigated potential immunogenicity in the two patients who discontinued? So first of all, I'd say that the two patients that discontinued didn't have any particular underlying factors that would lead us to believe that they were at risk of this of the events that they had. Typically, evaluation of things like anti-drug antibodies, the samples from the earlier stage clinical trials are banked until the assays are validated, and then they get analyzed at a later time point. So we don't have data on anti-drug antibodies in these participants, but from the other labs that we've seen, there was really nothing very remarkable. I would add that this is a biological, so DMD44 is a biological drug, and these kind of reactions are completely expected with biologicals. It's just part of the profile of these kind of drugs, and that includes all drugs. In fact, you can see these sorts of reactions even with corticosteroids. FDA were made aware of the event as pretty much as soon as it happened and didn't place any restrictions on the clinical trial at all. We were able to continue enrollment at the 5 mg/kg dose, and we were also able to dose escalate to 10 mg/kg. And of course, we haven't seen any similar events across the rest of our program or at the higher dose on this program. Thank you, Steve. So, the next question comes from Steve Seedhouse at Raymond James, and I'm gonna give you a break, Steve. We're gonna move it over to Mike Flanagan. Can you please elaborate on the normalization method to myosin heavy chain 7, and what the unadjusted, unnormalized data are as well to help contextualize data among competitive landscape? Yeah, it's a... That's a good question, Steve. So just to give you, I'll go a little bit on the inside. We'll stick with the baseball, or I guess we were doing hockey, but anyway, the- Hat trick is a soccer reference, just to say. We're gonna do football. That's right. Hat trick is a football reference. Anyway, just to get back to the question, so just to give you an insight, so we take an open biopsy from the bicep. Part of it goes to a digital droplet PCR, which we think is the gold standard to evaluate all exon skipping, so we've used digital droplet PCR. Another part of the biopsy then goes to immunoblotting, which is also called Western blotting, and this is where you run the protein from the biopsy on a gel, and then you look to see how much is produced, dystrophin is produced compared to a control set of dystrophin, and then it's calculated as% of normal. And then within that gel, you also have internal controls. So the internal controls are muscle-specific proteins. That would be myosin heavy chain is used, as well as alpha-actinin. So those two controls allow you to control for muscle content and loading onto the gel. So the way that we've presented our data are just straight up normalization to those internal controls. There's no additional multiplication due to muscle content. Sometimes you've seen in press releases or presentations, a muscle content factor. We have not included that. We believe that the addition of that factor is like double dipping. So if you've normalized on a gel, that already normalizes the amount of muscle content that you have with myosin heavy chain. There's no need to multiply by a muscle content factor later on. So that's the way that we presented the data. The data are represented as essentially 0%, which would be no dystrophin, to 100%, which is normal. So the normal is calculated by taking samples from healthy individuals and then loading them on a gel for basically a quantitative analysis. So that's the way that we've calculated. We use a common lab, AGADA, which is the leader in the determination of dystrophin. Majority of people that are running DMD trials use AGADA, so they're well known and respected, FDA inspected, confirmed. So that's the lab that we use. Hopefully, that answers Steve's question, probably more than he wants to know. Good job, Mike. Thank you. Okay, now, the next question, or a couple of questions, come from Yanan Xu at Wells Fargo. First of all, he does also congratulate us on the data. Steve, I'm coming back to you. Given the high levels of skipping and dystrophin expression, curious if you have seen any functional changes in del-zota patients? As I alluded to a little earlier, we've definitely seen some encouraging trends in the data that we've looked at. This is actually a quite an early time point for this disease, and so we didn't feel that the data at this point was mature enough to share externally. But, as I also mentioned, the very profound changes and early changes that we've seen in creatine kinase do indicate that we're affecting the disease biology in a very positive way, and we would anticipate that we'll see changes in the functional endpoints as we follow the patients a little further out in time. Okay, and sticking with you, Steve, a follow-up question from Yanan on the safety: How would you mitigate this AE in further studies? I'm assuming that Yanan's referring to the anaphylaxis event that we saw. Yes. OEPs, yes. Really, anaphylaxis is one fully expected with biological drugs. It's been seen with many, many facts, basically, just about every drug that's on the market, an anaphylaxis-type reaction. So these are really idiosyncratic reactions. There isn't anything that you can do to mitigate against them. Most drug labels would include a caution or contraindication to patients that have a known hypersensitivity to the drug or any component, any component, such as the constituents of the drug. But in clinical trial setting, these are just things that happen. I think it's important to remember that this is most likely to be due to the antibody component of the drug. RNAs are pretty inert, and particularly PMOs are charge neutral and have a very good track record with regard to hypersensitivity-type events. So, this being almost certainly attributable to the antibody, allows us to look across all of our safety experience, and we've dosed over 100 patients now with this platform. On the del-desiran program, everybody's through 18 months of continuous dosing, with many patients through two years of dosing. On the FORTITUDE program, we've got several patients that are through at least one year of continuous dosing, and we haven't seen any such events on other programs, and we've only seen one event on the del-zota program. Thank you, Steve. And now just back to whether hat trick is a hockey term or a soccer team term. Steve Seedhouse reminds me that there is an NHL hockey player. His last name is Del Zotto, so maybe it's a hockey term. Okay, moving to the next question, from Gavin Clark-Gartner from Evercore. Another question on the anaphylaxis. Could there be any mechanistic link? No, not at all. So anaphylaxis type reactions are typically mediated through IgE. Patients that experience them have a true allergy for want of a better word, but they're just hypersensitive to the drug. It triggers mast cell degranulation via IgE. It's a very well-known mechanism, and there isn't really any component of the drug that would place any participants at high risk for this. Thank you, Steve. So this next question, I'm not sure if it goes to Mike or Steve or both, but it comes from Tazeen Ahmad from Bank of America. Given the background expression of dystrophin in these patients, how would you define their clinical manifestations of DMD symptoms at baseline for patients with more severe exon defects? Steve, you want to, you want to take that as kind of a- Yeah. Can you just read that back again, Mike? Yeah. There was multiple parts to it. Given the background expression of dystrophin in these patients, I'm assuming meaning DMD44 patients, how would you define their clinical manifestations of DMD symptoms at baseline, at, versus patients with more exon, severe exon defects, which I'm assuming is lower, lower dystrophin? Yeah, so, that's actually quite a difficult question to answer because, it's not really an apples to apples comparison. In our study, we've enrolled a broad range of patients, from 7 years of age all the way up to 27 years of age. Typically, that isn't done in other clinical trials, so the baseline characteristics of the patient in terms of their ability to walk, their weakness in muscles beyond the legs, et cetera, is driven by how long they've had the disease. Generally, patients with exon 40, with DMD that's amenable to exon 44 skipping, because they do have some background skipping and some background low-level dystrophin production, their disease does move just a little bit slower than other forms of DMD. So, for example, they lose ambulation a couple of years later. That said, it's still a disease where, just about everybody is gonna end up losing ambulation completely, so they'll become wheelchair dependent, and DMD44 is still a form of DMD that causes a considerable reduction in life expectancy. So definitely a severe disease, but it does just move a little bit slower than some of the other exon skipping amenable forms. Thank you. Steve, I'm gonna come back to you. A question from Joey Stringer at Needham, which is just, given the discontinuances, is there a chance that we would modify our protocols in additional studies, such as using pre-treatments? No. Across the platform, we've really not seen a high incidence of infusion reactions, and as I said earlier, this is the only case of anaphylaxis that we've seen, and these are entirely expected with biological drugs. We don't mandate pre-treatment across the program, but we do allow our investigators, if a patient has, for example, an infusion-related reaction, an increase in temperature during infusion, et cetera, to administer pre-medication at their discretion. So it's something that the investigators can do if they want to, but we don't feel the need to have this given routinely across the platform. Okay, we're at time. There is one last question from Ritu at Cowen. Was the 7% of mean baseline at placebo higher than expected? I think, you know, based on our-- based on the literature, it was, it was thought to be around 3%-7%. So I think it's, you know, it's in the same range that we would have expected for, exon 44. And as Steve had indicated, it's known that those patients have slightly more exon skipping, like intrinsic exon skipping and production of dystrophin, and that's why a number of people told us, too, that that was gonna be really hard to demonstrate increases above that. But as you saw today, we've seen, dramatic increases in both exon skipping, well above background, statistically significant, as well as statistically significant dystrophin production. So, the data for the placebo are right in line with our expectations, and treatment with del-zota provided that increased improvement, in skipping and dystrophin production. Okay, so with that, I wanna thank everybody for the questions, and you know, turn it back over to Sarah. Thank you, everybody, for joining us this morning. As you can see, we're thrilled with the data that we have observed, both from a delivery to exon skipping, to the increases in dystrophin production, to the changes in serum creatine kinase. Our job now is to execute and to complete the study, and then also we're really looking forward, as we've said, to regulatory interactions to understand what can be the most expeditious path to accelerated approval. Once again, we've connected the dots. We did it with del-desiran, we've done it with del-brax, and now we've done it again with del-zota. Our vision and mission remains the same: to make a profound impact in people's lives by revolutionizing the delivery of RNA therapeutics. Today, we're even one step further with that vision. Thank you so much for your time this morning, and with that, we'll close out the call.