Thanks for having us, Mari. Really appreciate it. And we're doing a fireside chat format. So maybe to start off, for those who are new to the company, if you can provide a quick intro to Mereo. Yeah, so Mereo has two rare disease programs, both late-stage programs. The first, which is probably garnering most of the attention at the moment, is for osteogenesis imperfecta. So we have setrusumab, our anti-sclerostin inhibitor for brittle bone disease or osteogenesis imperfecta. And this is in two phase III studies being run by our partner, Ultragenyx. The first is in five to 25-year-olds, and the second in two to five- year-olds. And those studies are fully enrolled, which is very exciting. We expect to have the data in 2025. The second program, which is alvelestat, our neutrophil elastase inhibitor for alpha-1 antitrypsin deficiency. So this program, we completed the phase IIs. We've been getting the program phase III ready. So we're on track to get that ready around the end of the year. And then starting the phase III will really be waiting for the funding. Got it. So we've been doing a partnering process in parallel with getting the program phase III ready. The key about both of these programs, so they're both new mechanisms of action in the diseases that we're looking at. They're both large market opportunities. So we're looking at over a billion-dollar market opportunity for each of them. And the other key thing that we have focused on is ensuring that despite these being a rare disease and you have a limited number of patients that you need to have in these studies, that we really focus on the clinical outcomes that matter to the patients, to the physicians, and to the payers. And you'll see that runs. So even with our AATD, we're not focused on the level of AAT in the blood. What we're focused on is the clinical outcomes. And that's been a true theme throughout our programs. Got it. Yeah, I think that's a great intro and to set the stage for OI and the ongoing pivotal studies. This program's partnered with Ultragenyx. Maybe talk about that collaboration and the economics as well, and talk about the plans for the commercial opportunity. Yeah, so Ultragenyx are running and leading the global pivotal studies, the two studies I mentioned, Orbit and Cosmic. But this is a collaboration. They're funding those studies, fully funding those studies, and also the CMC activities. But this is a true collaboration. We have joint committees for everything: regulatory, CMC, development. We have a joint steering committee, a joint commercialization committee. So I think at the moment, there isn't a day goes by when the two teams are not talking, given the stage of the program. In terms of the economics, so we have $245 million in milestones to come. And we believe we will get most, if not all of those milestones based on where we are and the forecast. We have Ultragenyx on their territories. So we own the EU outright. On our territory, we pay Ultragenyx a flat double-digit royalty. On their territories, the rest of the world, they pay us a tiered double-digit royalty. And again, we believe we will reach the top tier of those royalties, which is higher than our flat double-digit royalty. Got it. Okay, that's helpful. And is there anything more you're seeing about the triggers for the milestone payments and also for the tiering for the U.S. royalties? No, I mean, on the royalties, as I mentioned, we really believe we'll get to that top tier of royalty, which will be a very good royalty income for the company. And obviously, that goes straight to the bottom line. And then on the milestones, there are some pre-commercial. They're not all commercial or sales milestones. So there are some that are pre, but we haven't defined or broken those out yet. Got it. Okay. And maybe talk about the OI market opportunity in the EU5 region that you're focused on and what proportion of OI patients could be addressable by setrusumab at launch based on your market research and pre-commercialization efforts? Yeah. So the analyst consensus for setrusumab in OI globally is anything between $1.2-$2 billion. And we use Crysvita as a good analog here. It's lower prevalence. It's 46,000 rather than more like 60,000, arguably a slightly less severe disease than OI. In Europe, that is forecast to get to EUR 500 million. This year, the forecast from Kyowa Kirin is just below EUR 350 million. So that's a very good analog. And EUR 500 million is a very good market opportunity for a European product. So if you look at the potential milestone and royalty stream from Ultragenyx and then combine that with the potential revenue from the European opportunity, it looks like a very good P&L. And I know we're going to talk about the infrastructure you need in a little minute with respect to the OpEx. And then in terms of the addressable population, so the estimates for Europe are around 25,000 patients. And in the phase III, we are treating the type one, the type three, and type four patients who represent around 85% of that number. And there are some publications out there that type one, they are the least severe, I guess. But there are a group of type one patients who fracture quite a lot. So it's not that they don't have fractures. They can fracture quite a lot. And then the type four can be wheelchair bound, can have scoliosis, spinal problems. And type three is the most severe. So type three, wheelchair bound, scoliosis, can have respiratory problems, very short stature, and many fractures. So type one who's fracturing a lot could have two or three fractures a year more. Type four could be two. Type III could be Type IV plus. And many more, actually, because they don't report the fractures, as we found out. In terms of the addressable population, what we've been looking at in the key EU5 is doing some patient finding. We're not having to go out and find the patients, but going to the centers where these patients are treated in the key EU5. And what we're actually finding is that in some cases, the pediatric patients in particular, there are a higher number than the prevalence numbers would suggest. And for the adult patients, there can be a lower number than the prevalence numbers would suggest. But overall, we actually believe the prevalence is going to turn out to be higher than the published estimates. In these treatment centers, we found 5,000 pediatric patients and 5,000 adult patients. These are patients who are going in to see their physicians because of their problems with OI. If you like, that is a very strong indication of a treatable population. Got it. And this is based on data that you're getting from the EU, kind of like US claims data? It's not U.S. claims data. We actually go into the centers and look for the patient data. So it's patient-by-patient data. Got it. Interesting. And maybe kind of a good question, segue question there. If you launch this, you've got these patients on the radar, do you think there's going to be a bolus of patients with the launch that would want to go? We do expect there would be a bolus of patients, yeah. I mean, there are some. We did this in Milan recently, so we are doing some media awareness campaigns with the KOLs to raise the awareness of OI within some of these European countries, but we do believe there would be a bolus of patients from the get-go. Now, of course, we're going to launch in Germany first. That's where we'll first get reimbursement. Got it. Okay. And what's the reception been like from payers? And do you have an indication of how pricing and reimbursement could look in the EU5, particularly taking into consideration fractures as an important endpoint for a patient versus something like a surrogate? Yeah. I mean, again, going back to the introduction, we're studying fractures, and that's what matters to the payers. The PRO always also matters, how the patients are feeling. We have some PROs as a secondary endpoint, and mobility clearly matters, especially for these younger patients. If we have the opportunity to treat these patients from two up and really impact what happens with scoliosis, whether they need to be confined to a wheelchair or not, that's hugely impactful from a payer perspective. So we have taken scientific advice already from the G-BA in Germany, and we've also had scientific advice from NICE. So both ends of the spectrum in terms of the payer discussions, if you will. That's given us our envelope for these pricing and reimbursement discussions. Excellent scientific advice from both authorities, and so we're using, again, Crysvita as an analog here. One of the things somebody was asking me earlier, why can't you just price it much, much higher? Why do you have to price it lower than the U.S.? We do have in Europe budget caps. If you go in with a price that is really high and you hit that budget cap, you're going to really struggle with your pricing discussions. You want to go in with something that's reasonable that will keep you inside that budget cap. Crysvita, EUR 60,000-EUR 80,000 a year. Got it. So that's probably the best analog. It's a base case, but that's net, right? Right. So each country you go in and negotiate. And as I said, we'll start with Germany. And we'll start with pediatrics. It's a weight-based dosing. So you want to start with pediatrics. And we'll start with Germany. And then so Germany could well be much higher than that. And then you negotiate your way through. Got it. And for potentially justifying a higher price, can you collect data on how much it costs to manage patients, especially like Type III patients? And what do those costs look like? And does that support that argument? Yeah, we're using all of that to support the pricing. The other key thing that you need to do and that we've had discussions around with the scientific advice is what are you going to do downstream to protect your pricing because you have to go back with your real-world evidence. And so we're setting up the registries, the systems right now so that we can collect that real-world evidence and really support the pricing downstream to maintain it. Got it. Okay. And what's your expectation for approval timeframe, assuming one of the interims hits? And then how long would it take for country-specific reimbursements to kick into place? Yeah. So that's an exciting question, Rory. So if either interim one or interim two hit, then those would be in the first half of next year. Actually, the interim one sort of spans over the end of this year, early next. And interim two would be in Q2 mid-year. So if we hit either of those, then we would expect to get approval in 2026. And then in terms of launch, Germany would be first, as I mentioned. And we can launch in Germany pretty quickly after approval. And then the next countries in the sequence would come online within the next 12 months. Got it. Okay, that's helpful, and let's talk about the studies. What are some of the key points investors need to know about the studies? There's been a lot of discussion around the types of patients that you enroll into the study, discussion on baseline fracture rate, and also Type III and Type IV patients, those proportions. How should investors think about that, and what's the latest you're saying there? Yeah. So in the phase II Orbit, which previously did the phase III, it was a phase II, phase III. So in that one, we saw a 67% reduction in fracture. That was comparing post-treatment to pre-treatment. That was at six months, and it was maintained at 14 months with very good stats. Now, in that study, it was a 24-patient study. It was really a dose-finding study. In that study, there were about 1/3, it was seven patients out of the 24 were Type III, IV, which are these more severe patients. In the phase III, we actually have more like 50-50, so more like 50% Type IIIs, IVs. So clearly, that could drive up the baseline fracture rate. The other thing is that with the phase II, pre-treatment versus post-treatment, we were relying on the medical records of the patients to determine the pre-treatment baseline. Those are radiographically confirmed fractures. As we know, many of these patients get on with their life. They have a fracture. They know they've got a fracture. They don't bother going to the physician to have it radiographically confirmed because they know. That pre-treatment baseline annualized fracture rate, which was 0.72, median 0.72, could well be much higher in the phase III patients. That is the first thing. We are actually expecting the annualized fracture rate for the placebo group in the phase III to be much higher than the phase II. The second is we have investors who are trying to guess, will we hit interim one versus will we hit interim two? Interim one is a very high bar. You have to hit a p-value of 0.001. It is only using 2% of the alpha. So then investors say, well, why are you doing it? And the reason is if we are able to reproduce, let's say, the 67% treatment effect that we saw in the phase II, and we have a much higher fracture rate in the placebo arm, it may be that very early on, we can see that difference with those sorts of stats. And these are children on placebo. They're not getting their bisphosphonates. They're on placebo. So it makes sense both from that perspective, but also from our perspective of getting to that filing as soon as possible to do these interim analyses. Interim two, we feel very confident about interim two. It'll be around the 12-month treatment point. The p-value needs to be 0.01. So we have a very good shot at hitting that. Got it. Yeah. Makes sense. The first interim is definitely a higher bar there. It seems like if that does hit, that'd be pretty impressive if that happens. Yeah. I mean, the one thing that we also need to know, if interim one doesn't hit, it doesn't mean that there isn't a very good treatment effect. It doesn't mean it could still be 70% treatment effect. And it might be, for example, that there's just more variability patient to patient. So you can't see that signal and you need longer. It may be that the curves need longer to separate, for example, the placebo and the active. So it doesn't impact. It shouldn't impact on how investors think about the efficacy. Got it. And Ultragenyx has mentioned that the first interim is at least partially predetermined based on accrual of 60% fractures. How was that threshold picked? And what is the annual fracture rate assumptions for treatment and control arms at the first interim? Yeah, so the first interim was, it's actually time-based, so when might you have expected to see that 60% of those fracture events? But it's time-based because it's operationally easier to do it that way, and so 60% and the second interim is 80%. Got it. Okay. Yeah. Okay. That's helpful. And can you give us a sense of how much larger treatment effect and how many more fractures, both relative to the phase II data, would be needed to succeed in the first interim? At that first interim, it really does depend on what the placebo baseline fracture rate is. So the higher the placebo baseline fracture rate is, the lower treatment effect you can detect earlier, right? And it also depends on the variability. The higher the variability, the longer you're going to need to see that treatment effect. So yeah. So it really depends on all of those factors. So I can't give you a specific treatment effect. If you had the same baseline as placebo as the 0.72 median in the phase II, then at that first interim and the same variability, you would need slightly higher than the 67% we saw. Got it. Okay. But there's a lot of moving parts, so. Okay. Well, definitely an exciting update ahead. This may be the last question for OI. Just talk about the unmet need there. What do patients currently use, and how do you see positioning? Yeah. So patients are currently given bisphosphonates. Not all patients, but many patients are given bisphosphonates, especially when they're children. The bisphosphonates are thought to help with fractures a little bit, although the studies are very, very mixed. And they also help with pain. So that's the standard of care apart from the usual surgeries, etc. And the patients going into the phase IIIs, many of them have been actively fracturing on their bisphosphonates. So in the phase III ORBIT, they have to come off their bisphosphonates to go into the study. But they have actually been fracturing on their bisphosphonates. So some of the physicians have said to us, "Look, if you get these sorts of reductions in fracture and that carries through, this is a game changer for OI. Got it. Okay. Really helpful. And so let's move on to alvelestat. Talk about this program, the value proposition there, and how investors may not be fully appreciating the AATD opportunity with this drug. Yeah, so we're focused on the lung disease in the severe alpha-1 antitrypsin population, so these are the PiZZs or the Null s who have low or zero AAT, and it's an oral molecule, oral neutrophil elastase inhibitor. We ran a phase II, which was a biomarker study. There were two phase IIs run. One was an investigator-led. There were two things about the phase II that are important take-home messages. The first was that we showed changes in the St. George's Respiratory Questionnaire that is typically used as a secondary in COPD studies, so this is a PRO-like instrument, and we showed clinically meaningful changes in that PRO instrument. That has not been done with the current standard of care, which is augmentation, and the second is that we also enrolled earlier stage patients in that study. So these are patients who have been genetically diagnosed, but they may not have lost so much of their lung function. So they may have 80%-85% of their lung function versus augmentation where the studies have typically been done 65% or lower. So an earlier stage patient population where in oral therapy like this, a daily oral therapy could really fit the treatment paradigm. And so, as I mentioned, a lot of the other AAT therapies, they're focused on AAT levels and getting to maybe to 11 micromolar. But we don't actually know what level of AAT is really needed to drive these clinical outcomes. And so augmentation so far, it's not reimbursed in many countries in Europe because of the lack of clinical outcomes, positive clinical outcome studies. So that's why we're really focused on these clinical outcomes. Got it. And maybe talk about the phase III plan and what you have gotten alignment on here. Yeah. So we have now very detailed alignment, which is proper alignment with the FDA on the use of the SGRQ score as the primary endpoint with a shuttle walk test as a key secondary. With the EMA, we have alignment on lung density by CT with a p-value of 0.1 maybe being acceptable. So one global study around 220 patients, 12 to 18 months. And we've been working with both agencies to really get this detailed protocol agreed, which is where we are, and which is why I said phase III ready, now subject to funding around the end of the year. Got it. And you're also in conversations with BD partners as well with this one. Any status update there? Yeah. The discussions are continuing. The one comment I will make is we probably have about as much momentum as we've had in this process. So yeah, making good progress. Okay, and I think we're out of time, but if you can talk about cash position and key catalysts ahead that investors should focus on? We just did our Q3 earnings, just over $80 million in cash on the balance sheet. That will get us into 2027. Even if we have to wait for the very latest study readout from setrusumab, the phase III into Q4 2025, we've still got plenty of cash to get through that catalyst. That does not include any milestones or any potential partnership income from Alvelestat. We're in a very good place and have a very exciting 2025 ahead of us. Denise, thanks so much for joining us today. Thank you.