Thanks for standing by, and welcome to today's Syntara Investor Webinar. Presenting today is Syntara CEO Gary Phillips, and he is joined by Professor Claire Harrison, Professor of Myeloproliferative Neoplasms at Guy's and St Thomas' NHS Foundation Trust and a key opinion leader in this field. All participants are in a listen-only mode. There will be a presentation lasting for approximately 25 to 30 minutes, followed by Q&A, with the total duration being 40 minutes. If you have a question you'd like to submit, please feel free to type it in using the Q&A function within Zoom. It should be noted that today's webinar is intended to be solely focused on the announcement of the data rather than other corporate activities of Syntara. Please also note this session is being recorded, and the replay will be available shortly after the conclusion of this session. I'll hand over to Gary to begin. Please go ahead. Thanks, Matt, and welcome everybody to the call. Thank you for sparing us some time. It's been a busy day here in San Diego, but we're really pleased to share a bit of time with you and talk through the announcement that we made and the results that were presented at the American Society of Hematology today. Just before I go on, just a forward-looking statement and just to note that the results presented today at the conference were interim results. We expect further interim data to be released in the first half of next year and final data in the second half of next year. So just as a reminder for those of you just joining us, and I'll be very brief here, Syntara is an Australian clinical stage drug developer. We've got three different drugs in phase 2 trials that are going to produce results during the next 12 to 18 months. And the first of those is what we're focusing on today, SNT5505, in myelofibrosis. We are a company that has attracted significant institutional investors. 52% of our register is institutional, with a lot of them being specialist healthcare investors. And some of them have invested quite recently in other companies which have exited with myelofibrosis assets, which is the disease area that we're going to be talking about today. So a really knowledgeable investor group. And the pipeline we've got has come from our in-house drug development group, which has done a great job at taking our drugs through pre-clinical and getting them into the clinic. Clearly, the stock price has increased in recent days and closed at $ 0.067 last Friday, as people are anticipating the results today, and I'm going to be very pleased to show you those results now, so this data today was presented during an oral presentation. It was a bit of an honor to get an oral presentation, a lot of our data is presented on posters, people walking past, so it was to have somebody there in a plenary session and having Q&A afterwards was great to see the attention that the drug is starting to attract within the hematology community. The American Society of Hematology is the world's largest hematology conference, and it attracts over 30,000 people each year, and it's a very busy place at the moment, so myelofibrosis is a disease which, for patients who have it, has a life expectancy of around about five years. Current treatments of this disease, which is characterized by a lot of fibrosis in the bone marrow. These patients have about five years to live. The bone marrow is your body's blood production unit. So these patients often suffer with cytopenias, low red cells, platelets, white cells. JAK inhibitors are really good at controlling the symptoms of the disease, but they're also not very well tolerated. And they do nothing about the underlying causes of the disease. And when patients fail eventually to come off of a JAK inhibitor, they often have about a year to live past that point. So there's a huge unmet need for additional drugs that will work alongside a JAK inhibitor, on top of a JAK inhibitor, to help these patients not only live a better life, but hopefully in the end, a longer life as well. We've been working on developing our drug in this particular disease for some time now. 5505 is an inhibitor of an enzyme called lysyl oxidase. Lysyl oxidase is a family of enzymes which are involved in the cross-linking of collagen. That cross-linking of collagen causes scar tissue or fibrosis tissue, which fills the bone marrow and stops it doing its job. The drug also has an intracellular effect as well and impacts on PDGF signaling, which also has an impact on the proliferation of cells in the bone marrow as well. So two different actions. We've shown quite clearly that in pre-clinical models that this drug is quite effective in myelofibrosis, but this is now. We're into the clinic and seeing what we do with patients. We've already trialed this drug once in patients that had failed on a JAK inhibitor, were ineligible to receive a JAK inhibitor. That study was reported at the American Society of Hematology last year. In that study, we showed that our drug is really effective. When a patient takes 200 milligrams twice a day, you see very effective inhibition of lysyl oxidase in the blood. So we know that it really inhibits the enzyme. That study also showed that the drug is very well tolerated and showed some encouraging signs of efficacy in what is a very difficult patient group and those patients that have already failed on a JAK inhibitor. So we took that data back to the FDA at the end of 2023 and then commenced a study, which is this one here, where we're using our drug on top of ruxolitinib, which is the most commonly used JAK inhibitor. In these patients, they had to have three months on a JAK inhibitor on ruxolitinib before they started the study, and they had to be on a stable dose, so we're trying to control the baseline of the patients coming in. We also said that they had to have a symptom score of at least 10. Now, the symptom score in myelofibrosis patients goes from 0 to 70. It's a scale. Anybody over 20 is considered to have quite a significant disease burden, and I'll show you in a minute the patients that actually are in the study and where they ended up with. The results we're going to show you are around symptom score, and here, the endpoint in symptom score is we have to show that these patients have a 50% reduction in their symptom score in order to be called a responder. We call that a TSS 50. We're also going to show you spleen volume responses. Patients with myelofibrosis often have a very enlarged spleen. Most normal patients would have a spleen size of around, say, 300 mL. A myelofibrosis patient may have a spleen size ten times that size over three liters. Those patients, we need to show an improvement or reduction of 35% in order for them to be shown as a responder. We're also going to show you some results on the hematologic or the blood counts of these patients as well. So with that, we'll get into the study. Now, the patients that we had in the study, there were 13 patients who've reached 12 weeks, eight patients who've reached 24 weeks, and five patients who've reached 38 weeks. So as I said, this is interim data. This study is still ongoing. Those patients will continue until they reach 52 weeks on drug. We've had four patients have discontinued as of the data cut for the ASH presentation. The patients that are in the study, in general, I think are at the more severe end. They have a history of 38 months on RUX treatment, so about three years history on ruxolitinib. That's quite a long time. It indicates these patients are perhaps more at the severe end. Indeed, their symptom scores, there's a median of 23, which again indicates that they're patients who have a significant disease burden. Looking at the safety of the drug, I think in brief, we could characterize it as the drug is very well tolerated. We've had no serious adverse events that are drug-related. This does begin to make it stand out against the other drugs which are on the market and in development for myelofibrosis, where there's often cytopenias caused by these patients, the hematological toxicity. We're very pleased to see that the good safety profile that we saw in the monotherapy study that we reported last year has thus far been repeated in this study where we're using it on top of ruxolitinib. Then the first results on that symptom score, and again, I remind you that we talked about TSS 50, and there's a line on this chart on the right. Each of those bars represents an individual patient. The numbers along the x-axis are the symptom score that those patients started with. So if you go right to the right-hand side, you'll see a patient there who's got a symptom score of started with 10, and after 12 weeks on drug, has gone to 0. Another patient in the middle, say, has got 16 and has just gone down to about 8, so has had a 50% reduction. So all of those patients who've gone below the TSS 50, we would call a responder. So we were pleased to see that. But I guess after three months in an open-label study, we also thought that these patients, it's a drug that's being quite well tolerated, so it's not making them feel worse. It's a honeymoon period. They're feeling maybe good that they've joined a study. We take that with a little pinch of salt and really interested to see what happens to these patients when they get to six and then nine months. This is the chart showing what happens to them at six and nine months. The blue bar, again, is the patients at 12 weeks. The gray bar is what happened to them at six months, and then the purple bar at nine months. I think what we're really pleased to see here, that overall, about 60% of them have reached that TSS50 mark, which is a really good outcome for those patients. On top of that, that we're seeing patients improve the longer they're in the study. In general, what we see is an improvement from the six months to the nine-month period, which is really encouraging and backs up our hypothesis as to what we have here is a drug which is well tolerated that patients can take for longer, and the longer they stay on, the better they feel. We also looked at the spleens. Again, this is, I think, a very encouraging response so far, interim data. Again, what we're seeing is, in general, patients improve as they go from six months to nine months on therapy. We are reaching SVR 35 in some patients. I think two out of those 10 patients have reached an SVR 35, and three of them have reached an SVR 25. I think clinicians feel that particularly in this patient group, which is suboptimal, so patients who are struggling on ruxolitinib, you'll see that an SVR 25 is actually still clinically significant. Looking at the bloods, this is an emerging story, I would say. We didn't have many patients who were actually transfusion dependent. We can see a hint that maybe patients who are transfusion dependent are getting better the longer they stay on drug. But this is an area that we're watching closely and seeing this full story that emerges once we have more patients on drug between 6 and 12 months and particularly about 12 months going forward. Finally, this is the results for just the patients that have reached nine months. So four out of the five patients that have reached nine months' worth of therapy have reached that TSS 50. That's a really good result. Again, it's small numbers. We're waiting to see what these patients do when they get to 12 months. If we can keep them at that level when they get to 12 months, then that would be a really good outcome. And similarly, with the spleen volumes, we're starting to see significant changes in the spleen volume. Some of these patients on the right-hand side there have been on ruxolitinib for five years and have significantly enlarged spleen. So really not much else that can be done with them on the existing JAK inhibitor. And then after nine months on our drug, they've had a significant response in the spleen side. So I think that's a really encouraging point going forward. Now, the question is, how does that compare with other drugs? And again, there's nothing perfect when you come to this, but we've taken the drugs which are ahead of us in the clinic. And there's three of them there: pelabresib, navtemadlin, and that, navitoclax. And we've just taken the results that they had in phase 2, open-label results in a suboptimal patient population. So we're trying to compare like with like. And I think in general, in those studies, what they saw at six months' treatment was, in general, around about a 30%-40% improvement in TSS50, 30%-40% of patients reaching a TSS50, and about the same 30%-40% of patients reaching an SVR35. So the kind of numbers, albeit small and interim data that we've got, where we've got patients, 60% of all of our patients reaching that TSS 50 and about 20%-30% reaching SVR 25 or SVR 35, shows that our drug, with a very good safety profile, has quite a competitive profile. It may actually offer something in the way of treatment in future for myelofibrosis patients that other drugs in development don't currently do. So that's the goal. It's what we're looking to achieve as we go forward and where the benchmark is. And what's the prize? Well, obviously, patients and offering a treatment which helps these patients at the moment, which don't have many treatment options. There's also a commercial prize here in the last three deals with companies acquiring drugs in the myelofibrosis space have all been done for north of $1.7 billion for drugs that have completed phase 3 clinical trials, so that's a study beyond where we are now, it's the study that we will do next, but there's a considerable benefit and value to shareholders if you undertake such a disease, and again, just remind you that some of the shareholders that are on our register were investors in some of these companies in the past, so they understand precisely what the commercial goal is and perhaps what's needed to be successful in this space as well, and I think that's why they've been attracted to us as an investment proposition. So just to conclude that ASH presentation, I think the data has been consistent with the monotherapy data that we've got thus far, a well-tolerated drug. When it's used in combination with RUX, we've demonstrated that that safety profile is still good. Despite the relatively small sample size that we have, the absolute improvement in symptom score and the number of patients who've achieved the TSS 50 goal is very encouraging. And I think we're also encouraged to see that the symptoms and the spleen volume continue to improve over time. I think we think that's quite a novel finding that there's not been many drugs in this space that when you treat them for a longer period of time, the patients keep on improving. Of course, that goes together with a well-tolerated drug to give it quite a nice profile for both clinicians and patients to consider. Now, interim data, the additional patients that we'll see coming in, and certainly in the first part of next year, will be very helpful. We think that will guide us to building a regulatory package for the FDA and putting to them the design of a clinical study to get a regulatory approval for the drug, and we'll seek guidance on that to that pivotal study, which we hope we'll get from the FDA by the middle of 2025, and with that, I'll finish my presentation, and I'd like to invite Professor Harrison maybe to give her thoughts on the. Sorry, slight delay with the audio there, so hello, everyone, so I'm Claire Harrison. I'm a hematologist working in London. I've got 20 years' experience as a consultant in this area, and this is my area of special interest. I've been involved in many drug trials in myelofibrosis and have a lot of patients on my books, and I do a lot of work with patient advocacy, so that's led me to sort of understand quite a lot about the clinical spectrum, but also quite a lot about what the patient need is from the perspective of the patients as well, so where we are with myelofibrosis in sort of 2024, heading into 2025, is in North America at least, we have four different JAK inhibitors, all with slightly different targets, but all broadly delivering some degree of spleen and symptom benefit for patients. Two of them also potentially targeting the ACVR pathway and delivering some benefit for patients in terms of hemoglobin, and they are, so ruxolitinib is the first in class, fedratinib is the second, and then pacritinib and momelotinib. But there's still a big area of unmet need for our patients. The average patient would stay on ruxolitinib for maybe three years. Their life will be prolonged by it. But ultimately, underneath, their bone marrow is still accumulating fibrotic tissue, and their disease is still progressing. Many patients will have to stop the JAK inhibitor. And the reason that they often have to stop is because they have sort of on-target thrombocytopenias, so low platelets, and anemia, and because the drug stops working for them. So for our patients, we really need something that's got a way of having traction on the basic biology of the disease. And one way of doing that is potentially by targeting the mutations. And we're a long way off a targeted mutational therapy, although there are some in development. Another way is to take a rational scientific approach like this one, targeting LOX. And so what I've seen here is impressive. And I like the fact that we've got monotherapy data. So there's a group of patients that have had PX-5505 on its own. So we can only say for those patients, the changes that are seen here are just due to this drug. And for me, as a clinician, that gives me what I would call a reason to believe that this agent may well be effective for these patients. So that was data that was presented last year at ASH. It was a slightly more complete data set, I would say, and we saw the fibrosis change there. What we saw this afternoon in what was quite a busy session was this data that you've seen just now. And I just want to emphasize to you that these patients who are on ruxolitinib, who've often been on it for maybe up to five years, I think one of your patients was, these patients are tough. They've got a heavy burden of disease. Their disease has been progressing underneath, and they've still got big spleen, and they've still got symptom burden. So what we've seen presented is, one, reassuring from a safety perspective. This drug is well tolerated for patients. If they weren't tolerating it well and they didn't feel some benefit, they would be stopping. Some patients are discontinuing, but I would say nothing more than the rate of discontinuation that we would expect and that we saw presented, for example, with navtemadlin, the MDM2 inhibitor, this afternoon, up to 60% of patients had withdrawn at the time of the analysis in that study. And so here, the data that we've seen, I think, is impressive. I think what we've seen is that clearly there is still, one, a residual unmet need for spleen and symptoms. And the symptom data is particularly impressive. I do like the fact that it's progressively getting better. And I think as the data was shown, that's good. I think with this agent, with this mode of action, we would expect to see slower changes in the spleen because, one, the patients already got some response from the ruxolitinib. And secondly, what we're expecting to see here is change in the bone marrow microenvironment, then also manifesting in a spleen change. So it's gratifying to see what we've seen today. A question I can see in the chat, but about what amount of spleen response would we expect to see on top of ruxolitinib. So just want to orientate you to the differences in the different data you may be looking at with different drugs and different companies. The data that's been shown today is for patients who have continued ruxolitinib. They haven't been washed out, and then this agent added. So this is in addition, so over and above. It demonstrates the unmet need, and it's demonstrating what I believe is the activity of this drug. So often in the second-line setting, we're seeing more now something expressed, which is SVR 25%. In terms of the threshold for symptoms, well, that's kind of a bit under discussion. We've seen some drugs failing in the front-line setting because they haven't significantly beaten ruxolitinib. But what I've seen today would make me willing to recruit patients if we have the study open in the U.K. We don't at the moment. I think there's a strong biological rationale. Toxicity looks good. And I'm really excited to see more data and understand what is the plan for next phase of development. It would seem to be logical to put it in combination, but I'm guessing you might come to that in question. Yep. Thank you. Happy to take questions now, Gary. Okay. I'm just going to take some of the questions that we can see in the chat one by one. So I think one of them I can see is, is Syntara on track for trial completion of this study in the second half of 2025? And the answer is yes. I mean, the patients are already fully recruited back in August, so that patient will reach 12 months in August of next year. I've lost the. I can read the questions back to you, Gary, just to make it a little bit easier. So once again, just as a reminder to everyone, if you do have a question you'd like to submit, please feel free to type it in using the Q&A panel within Zoom, and we'll get through as many as we can in the time we have left. Gary, the next one was, would the TSS minus 50% and SVR minus 35% potentially be co-primary endpoints in a phase three trial? And following on from that, what have been the gold standard primary endpoints in other approved drugs for myelofibrosis? Yeah. So we can talk about that in terms of the discussions we've had with the FDA. The guidance that the FDA have given us is that the TSS 50 is very likely to be the primary endpoint that is the standard that we would be held to account for in a phase three study. They would need to see a secondary endpoint which supports the primary endpoint. That's very much up for discussion. Spleen volume has been used very widely in many drug trials in myelofibrosis. Some of that comes from the fact that the primary impact of a JAK inhibitor is on spleen size. It's been a very common endpoint to use. When you add a drug on top of a JAK inhibitor, often they look for further improvements in spleen size. But I think the discussion with the FDA we had was that they understood that spleen size, while it's important, wasn't necessarily the most logical endpoint to use for a drug with the mechanism of a lysyl oxidase inhibitor. So I think the field is still open, and we will look at the data that we collect in the first half of next year, including the bloods and the spleens. And then we will propose to the FDA what we consider to be an appropriate primary and secondary endpoint. But almost certainly, the TSS 50 will be the primary endpoint at the moment. Thank you. The next question is, given the size of comparable clinical programs in myelofibrosis, what would the most likely ideal number of patients for a potential pivotal study be? Well, there's two things that guide us here. One is that you need to have a trial which is large enough to get a statistically significant outcome from it. And if we were to continue and have four out of every five patients having a TSS 50, you wouldn't need a very large study to get a statistical improvement. However, on top of that, the FDA do require to show a minimum number of patients to assure the safety of the drug. So we think at the moment, and this is only our working hypothesis, I guess, that a phase three clinical study would be in the sort of order of 300-350 patients randomized with probably two on active to one on placebo. And the study length would be something that we need to determine after we've seen the 12-month data, but it could be anything from six months to 12 months in terms of its duration. Thank you. The next question is, in terms of a better response from hematology results, what was the expectation there? And potentially, should there have been less dependence on transfusion? I think our drug, from the mechanism, we believe that it will gradually help the fibrosis in the bone marrow. And then we need to wait for the bone marrow, the microenvironment there that's improved, to actually start functioning again. And that's a question that we didn't know going into this study, how quickly that will happen. We're very confident that we do reduce fibrosis in the bone marrow. We've measured that already at six months in the monotherapy study. But in this study, with rux as well, how long before that impact on the bone marrow actually starts to turn into a therapeutic benefit that you can measure with the patients? I think we're beginning to see something in the data that we've got, but clearly, we need to wait for the full 12 months before that happens. It's quite different. I mean, many of the drugs I think that have been trialed in myelofibrosis have worked quite quickly, but they also bring their own toxicities as well. And again, I guess go back to that thing that a drug that's well tolerated can be taken for longer. And if it gradually builds up its efficacy over a period of time, then that's a good thing. So story on hematology is, I think, emerging. We certainly haven't got any hematological toxicity that we're showing, which is good. The majority of patients are either stable or improving in their red cells and platelets. And we need to see how far we can go with that. Thank you. The next question is, were there biopsies of bone marrow taken to measure BMF scores? Yes, there were. I might talk to Claire in a minute to give us her thoughts on bone marrow fibrosis and the value of that. But we've got bone marrow fibrosis biopsies taken at three months, six months, and 12 months. We don't have anything at nine months. That was done because of the kind of burden on the patient and not wanting to give them repeat biopsies every three months. But we've got an incomplete data set. So at six months, we don't have all the results back yet. Rather than give interim data, which we think at this point wouldn't mean anything, we will collect all of the bone marrow biopsies up to 12 months and then have them analyzed in one center to reduce the variability as much as we can before we can really characterize the impact on bone marrow. But I might just mute myself, and Claire maybe add a few thoughts on bone marrow. Sure. Thanks very much, Gary. These changes in the marrow for these patients take sometimes many years to develop. Even if we use an incredibly aggressive therapy, which 90%-95% of our patients aren't eligible for, which is very risky, bone marrow transplantation, by risky, I mean 20%-30% chance of death, even when we do that, the bone marrow doesn't really normalize for 12 to 18 months. Clearly, we would expect PX-5505 to have an effect on the marrow, but it will probably be a slow and steady effect. We know it's difficult to reverse even with aggressive treatment, and therefore, I think these early signs that are being seen with regard to symptoms probably are the type of thing that you would see early on. You might see some subtle changes in spleen. I just wanted to come back to that, actually, if you don't mind, and comment to say it's also important for these patients not to see worsening, so these are patients whose spleen is gradually, probably usually getting bigger over time, and their symptom burden's getting worse over time, so a stable spleen is also important here, so I wouldn't expect the spleen to change substantially, so this is why I think the data is impressive. Then finally, to comment on these changes in the blood transfusion and the hematology aspect, that probably won't happen from this mode of action until we've got substantive changes in the marrow, I think. To look at expecting a patient who's requiring very heavy burden of transfusions to suddenly require none, it is quite tricky. The subtle changes I might want to see early on would be, for the non-transfused patients, maybe a subtle drift up of the hemoglobin or the platelet count. But I think what I'm trying to say is bone marrow changes will be important because it's proof of concept, but we could expect it probably to take a while. The changes that we're seeing in the monotherapy, again, there are helpful for us. Thanks. Might keep it with you, Claire, at the moment. The next question's around, are there signals of disease-modifying potential here? TSS and SVR improvement over a longer duration of therapy. Is this normally seen? Well, disease modification is kind of the buzz phrase in this field at the moment, but it's also a bit of a hated phrase because we know what we want to achieve for our patients, but it's a bit of a holy grail. So we want to achieve eradication of the clone, that the bone marrow goes back to normal, that the spleen goes back to normal, that the patients don't have symptoms and they live. So that's like reverting everything to normal. So that's actually quite tricky. So the way that benefit is measured in this disease at the moment is with these two measures, SVR 35 and TSS 50, or this slightly modified endpoint, which is called absolute difference in symptom score. And there are really too few patients here to look at that in detail. And there's a good enough signal on TSS 50, to be honest. But those are measures that are used to judge the benefit of ruxolitinib. So that means ruxolitinib is hard to beat. And it also doesn't totally speak to the activity of drugs such as PX-5505, where we would expect to see some on-target disease modification like reduction of fibrosis. So I think in long answer to a short question, but I think this is evidence of benefit. Spleen reduction we know is a measure that indicates survival advantage for patients. But I expect the field to pivot gradually over time such that spleen and indeed symptoms will remain very important. I think Ann Farrell is really convinced on symptoms being important for these patients. I've been to the FDA myself with different companies a couple of times, and I've heard that from her. But I think over time, we're likely to want to see the changes in the bone marrow microenvironment, like fibrosis grade reduction for our patients. But for now, the readouts on spleen and symptoms and ultimately, perhaps hematological improvement will be important. JAK inhibitors get improved just on spleen and symptoms without hematological improvement, though. Hopefully, that's addressed the point and maybe any few that were lurking around on that topic. Thanks. Thanks for that. The next question's an anecdotal one. Have you had an opportunity to talk to any of the patients who have had a good response to the treatment? How did they feel about it? And could they tell a difference? Could they tell the difference it had made for them? I'm guessing that's one for Gary. We just need to do the fancy kind of muting and unmuting of the speakers because I won't have had the opportunity to talk to patients. But I can tell you while he's on muting that symptoms are a big issue for my patients. Their quality of life and how they live it is really, really important. Over to you, Gary. Matt, can you just repeat the question? Just with regards to, have you had an opportunity to speak to any of the patients who've been on the study? How did they feel about it? And could they tell a difference that he'd had made for them? I haven't talked individually to any patients, but the presenter this afternoon, Peter Tan, the investigators in the study meet relatively regularly and discuss the safety that they're seeing in the study and just to ensure that the study is worthwhile to continue. And I know that some of his patients, some individual patients there, I think one of the patients has had looking like they've got an improvement in the rate of transfusions, also benefiting from an SVR35 and symptom scores as well. So we do have not direct feedback from patients, but we do have clinicians telling us that they are seeing patients. Like I think I explained before, so when I think Claire's done this before when she's looked at our data and sort of picked out an individual patient and says, "Look, there's a patient with four years on ruxolitinib. Their spleen's enlarged and they've got a symptom score of, say, 30. I've got some of those patients in my clinic. And I know that it's very difficult to help them at that point. After that long on ruxolitinib, there's not." And then when you come along with a drug like this, and again, albeit with small numbers, you do tend to look at individual patients and say, "Look, that patient has actually had an SVR 35 and a TSS 50 after being four years on rux." And that does make an impact, I think, on certainly the way I feel about the drug. I love listening to clinicians actually pick out and say, "Look, I've got a patient here that I wouldn't have expected to respond, and they are responding." And if they didn't like it, they wouldn't stay on the drug either. And we've got some patients now coming up to that 12-month mark. I think next week, I think it's the first patient reaches 12 months. So we're excited to see that continuing benefit and how many more patients really get to that 12-month mark and on drug and are seeing real benefit after probably many years of struggling with just a JAK inhibitor. Thanks, Gary. And just to squeeze one more, and I think you touched on it briefly during the presentation, but are there any other similar drugs in development to your knowledge? And if so, what stage are they at? I'll start that, Claire. I may know of others, but I think we're quite focused on the drugs ahead of us in the clinic. And they're pelabresib, navtemadlin, and navitoclax. Navitoclax is from AbbVie. I think the results in their phase three study, they were pretty good on spleen volume, but I don't think their symptom score really reached it. It failed. So I think there's a question mark over whether myelofibrosis is the right indication for that drug going forward. Pelabresib looked really encouraging in its results. I think it had a good reduction in spleen volume. I don't think it reached statistical significance on their symptom score, but they still had quite an improvement in absolute symptoms. But they've had a safety issue that's emerged in the last, well, over the last 12 months, I guess. And there's certainly at the moment Novartis, which own the drug, are pausing and looking at their data more carefully. So the Kartos drug, navtemadlin, is one that's going into phase 3 at the moment, produces around that sort of 30% improvement in spleen size and symptom score of the sort of numbers of responders. It's a drug which also is, I think, probably not as well tolerated as our drug. So again, you've got to be careful not to compare apples and oranges, and we need to see more data from our drug. But I think at this point in time, given the limitations of the data, we think that we have a competitive profile, which if it plays out with more patients and more data, stands a chance of really helping patients in myelofibrosis and offering something which the existing drugs in development ahead of us don't really look like they offer at the moment. Thanks, Gary. Thanks to everyone for the questions that you've sent in. And I'll also add an extra thank you to Professor Harrison for her time today during what's been a very busy time over at ASH. But Gary, I'll just hand back to you to provide a closing comment. Just again, at this point, we also, as we did this afternoon, is to thank the clinicians and the patients that have been part of the study. It's great to see the support that we've got. One of the challenges ahead of us is a larger study to get the registration. Positive phase two data and having patients who are happy on drug and improving on drug and report that back to their clinicians is the best result we can get to encourage clinicians to put patients in a study when we go to a phase three thing. I think we are off to a really positive start. We were delighted to see the emerging data and particularly seeing patients get better the longer they are on drug against the background of a really good safety profile. So yeah, really looking forward to the next data in March and reporting more news flow as we go through next year. Thank you very much for your time. Thanks, everyone, for joining again.