Hi. Good morning, everyone. My name is Edward Nash, Senior Biotech Analyst here at Canaccord Genuity in Equity Research. It is my pleasure to have with us today the management team from Kiniksa Pharmaceuticals. This is the name we currently cover with a buy rating. Joining us from the company is Ross Moat, the company's Chief Operating Officer, and John Paolini, the company's Chief Medical Officer. I want to thank you both for joining us today. Thank you. So maybe to kick off things, could you maybe just give us a general 10,000 ft view background on the company, just with your therapeutic focus from both the clinical and research standpoint? Certainly will do. Thank you very much, Edward, and thank you to the Canaccord team for inviting us here today. It's a pleasure to be here. And thank you to everyone in the room, as well as online that's listening. John and I will be making some forward-looking statements today, which are subject to risks and uncertainties, a copy of which can be found in our SEC filings. Sanj Patel, our CEO, is not here today. Unfortunately, he could not be here, as him and his wife Kristen welcomed a new baby into the world just a couple of days ago. So it's John and I today, and hopefully we can answer all the questions that you have. So thank you very much for having us. Many of you may be familiar with Kiniksa at this point. We've been on the market for the last five years or so with ARCALYST. The company is about 10 years old overall. Really, it's been quite an interesting story over the last 10 years or so. We're an organization that likes to move rapidly, and we are very focused on growth and adding value across the years and the pipeline that we have. We are a well-capitalized organization that's been profitable, and we've said that we intend to be cash flow positive on an annual basis moving forward. We have ARCALYST on the market over the last five and a little bit years, which has been growing very well in recurrent pericarditis, and ARCALYST is an interleukin-1 alpha and beta inhibitor with quite impressive both efficacy and safety profile. That's been doing very well in the market since the time of launch, with very significant opportunity ahead. In Q2, our earnings call just a couple of weeks ago, we announced the net revenue for the quarter was around $243 million for Q2. That was a $29 million quarter-on-quarter growth, which was the largest quarter growth that we've had since the time of launch five years ago. As I said, the opportunity is still very substantial for what we can achieve within that marketplace with ARCALYST. The pipeline is also very strong. At Kiniksa, we have the KPL-387, which is another interleukin-1 alpha and beta inhibitor. We announced some of the phase II results, which were the dose-focusing portion of our overall studies in recurrent pericarditis just a few weeks ago. We can go through that data throughout the meeting today. We essentially announced that we were moving forward into the phase III development with the target product profile that we specified right up front, which is a monthly, potentially auto-injector formulation for an interleukin-1 alpha and beta. We are now moving forward into the phase III, and in fact, we have started, initiated the phase III study and are already dosing and enrolling patients, and we expect to be on the market, data willing, by the 2028, 2029 timeframe. We also have behind that KPL-1161, which is an Fc-modified interleukin-1 alpha and beta inhibitor with a potentially quarterly profile, which could have utility in multiple disease areas. The company is well-funded, well-capitalized, and very focused on growth for the years ahead. Thank you very much. That was a great overview. Maybe for those who don't know about recurrent pericarditis, could you just briefly explain how patients are identified, diagnosed, and their treatment journey for RP and kind of where Kiniksa's drug fits in? Thank you. Edward, maybe I will make a start on that. John, if you have things to add, then you can. Maybe if I just kind of ground us all in the size of the population for recurrent pericarditis. This is really a very severe, very debilitating disease for many patients. There are around 160,000 patients in any given year that suffer from pericarditis. Many of those patients just suffer as it is kind of a once and done type of incidence of pericarditis, albeit very debilitating during the time of that initial flare. Unfortunately, a proportion of those patients go on and suffer from recurrences over time, and that is where recurrent pericarditis comes in, and that is around 40,000 patients in any given year. That can then also be further subdivided between the number of flares that patients suffer, but ultimately, there is a 40,000 patient population in any given year that are suffering from recurrent pericarditis. Unfortunately, many of these patients, being a rare disease and a flaring disease, which is also very widely dispersed around the country, there is a lack of real centers of excellence per se across the country that are looking after this disease. Patients are very widely dispersed, being seen by many cardiologists, many rheumatologists. Unfortunately, what happens with many of these patients is that they get diagnosed later on in the disease, as well as going through misdiagnosis along the way as well. In fact, there is around 2.7 on average misdiagnoses before the patients get diagnosed with recurrent pericarditis. Increasing the education and awareness on how to identify this disease and obviously treat the disease now that there is an approved therapy on the market to specifically address the underlying mechanism of interleukin-1 alpha and beta of the disease. It is obviously very important for these patients to get an earlier and a timely diagnosis. That is generally the patient population, and what you may know is the treatment paradigm has changed quite significantly over time, whereas patients used to be treated often on the very first incidence actually with NSAIDs and colchicine, and then after that, moving forward to steroids, ultimately corticosteroid use, through having really a lack of other treatment options to try to control the disease. That has been changing very substantially over the last five years or so since the introduction of ARCALYST as the first and only approved therapy. We have seen lots of publications and guidance, for example, from the ACC, that have also been affirming that change in treatment paradigm, which is ultimately to opt for an interleukin-1 alpha beta inhibitor after NSAIDs and colchicine and prior to corticosteroid use. Fantastic. Thank you. If we just focus now on the multiple recurrence patient population, you guys have stated that you've penetrated this group by about 21% to date. Is this the group that makes up the majority of the revenue right now of ARCALYST? It certainly makes up a sizable portion, Edward. What we have said previously is that we are focused on the entirety of the 40,000 patient population. That's where we have the broad label for ARCALYST, and the label is completely agnostic to the number of flares a patient must have suffered before they get access to the only approved treatment. The data that we have provided externally is the penetration rate, as you said, Edward, into the 2+ recurrence group, which is a 14,000 patient group of the 40,000 overall. Clearly there are an even larger group of patients on the first recurrence, 26,000. We've said that we've been growing over time, and that we've been up to around 21% as of the end of Q2 penetration into the 14,000 patient group. Those with two or more recurrences. We also have seen growing utilization in the first recurrence as well, and physicians ultimately getting much greater comfort of how to prescribe a biologic and how to manage patients when they're on ARCALYST. Ultimately, taking the view that along with the ACC concise clinical guidance, as I mentioned as well, is ultimately why allow patients to suffer for more flares throughout their disease when there is a treatment option there to help them. The importance, and what we learn a lot from patients, is not only wanting to quickly, rapidly overcome the flare that they are often suffering at the time of prescription of ARCALYST. But the most important thing to patients is preventing future flares for the future. Ultimately having the knowledge that this is, once a patient becomes recurrent pericarditis, this is usually a multi-year chronic disease for most patients. ARCALYST has ultimately been designed to be utilized throughout the duration of the disease. Using it earlier on I think makes a lot of sense to help patients throughout the duration. Right. I ask the question because it seems that most of the conversations we have with doctors, and we're quizzing them on the IL-1 blockers, they're almost always unanimous about how effective they are, and that the drug is really They see it as extremely effective with their patients. I think one of the things I wanted to ask is, you mentioned about the meantime that a patient's on drug now is three years. Which is interesting because sometimes we get the question from the KOLs is that it's an expensive drug, which I never like to take the opinion of doctors on paying. You're not paying for it, right? It's insurance that's paying for it. However, you're seeing three years, patients being on drug for three years. You don't see any headwinds on the cost front, it seems, because your penetration's been increasing, is that fair to say overall? Yeah. So penetration's been increasing as we've said. Access through to the drug is very, very strong. Generally, patients' co-pays, particularly commercial patients, is generally $0. So the affordability to the patients is very good. What is very important to us and physicians, and obviously to the patients, is that when a physician identifies a patient as suffering from recurrent pericarditis and then they prescribe ARCALYST, that the patient gets access to therapy. So we see that generally across the board, and patients get good access. Often the co-pay is zero, as I've said. I think both payers and physicians now, and patients to an extent, understand that this is generally a long disease. As I said, ARCALYST has been designed to be used as a treatment throughout the course of the disease. That's been a substantial shift in the thinking of how to treat this disease, because historically, before ARCALYST was available, I think physicians would try to treat for as short a time period as possible. Treat through the flare and stop treatment, and then treat again if they flare again and again. But that's often through not having better treatment options. If you're using, having to opt for steroids, then it's very difficult keeping a patient on steroid for long-term with all the toxicities, all the different effects that that has on a patient. So the introduction of ARCALYST has now allowed for this treatment to actually be appropriate for treating throughout the disease. Knowing that at some point the disease ceases in these patients, and you can then adequately stop therapy. But up until that point, we try not to stop and start too much, and allow for treatment throughout the course of the disease. Since you have that three-year mean now of patients on drug, do you have any better idea of how long patients you think might need to be treated with ARCALYST before being able to come off? Yeah. It's very difficult to say overall. Yeah. There are publications and literature there to try to guide, and also looking at risk factors, which potentially could give some guidance at least to how long a patient may be suffering for from the underlying disease. But ultimately, when you look at some of the largest collections of data on this for patients that suffer two or more recurrences, the median duration of the disease is around three years. As you mentioned in your question as well, the average of ARCALYST treatments now is around three years. But this is the median of three years of the disease. That's because the largest publication trying to track the natural history of recurrent pericarditis and how long it lasts in patients with two or more episodes. Unfortunately, it goes through to around eight years. At the eight-year time point when that study stopped, it was still around a quarter of the patients that were suffering from the disease. We don't actually know what the average duration of disease is. We know that the median was around three years, so the average is probably longer. ARCALYST has now been used for an average of around three years, and we'll see how that changes over time. Yeah. We'll ask the question again another three or four years, and we'll have a better idea, right? Certainly data builds over time. I want to jump over to the commercial side now. Could you maybe just remind us of what your commercial infrastructure currently consists of, the number of sales reps you have out there, and given the fact that now you're seeing greater penetration into your target market, do you see any need in the near future that you'll need to upsize that? So it's something we've been focused on a lot. You've been following us for a little while, Edward Nash. You know that we are a very data-driven organization. We take capital allocation incredibly seriously, and our focus on driving value across the business. We don't share what the size of our sales team is. We haven't done that for many years. But yes, we're very focused on making sure we address the opportunity, as best as we can. Clearly, our sales team are incredibly important to do that and to disseminate data, as is our medical affairs team in the field, and to address the opportunity and increase awareness and knowledge on ARCALYST. So that is incredibly important, but we also focus on other areas as well. We've also recently launched a DTC campaign to patients, trying to identify recurrent pericarditis patients and to encourage them and empower them to go and speak to their physician about ARCALYST, because one of the things that we learnt is that actually around when you ask patients that are suffering from the disease whether they are unaidedly aware of ARCALYST, only around 14% of the patients were aware of ARCALYST as a treatment for the disease that they're suffering from. Yet when they go and speak to their healthcare professional and inquire about ARCALYST, it ends up in an ARCALYST prescription about 80% of the time. So in order to educate and empower patients, we thought that was something very important to do. We started doing that earlier this year with a very targeted DTC campaign appropriate for rare disease populations. And we do that a lot through AI and machine learning and other more innovative ways of being able to do that now, rather than big pharma commercial, big expenditure type of DTC. So we focus on things like that. But also peer-to-peer education is incredibly important. There are ultimately a multitude of ways of getting information out there to try and help this population, and we're focused on all of them. And do they tend to be more centers of excellence when you're trying to detail or that are out there that are treating RP, or are you getting down to the secondary, tertiary centers out there as well? Yeah. It is actually really across the board, across the whole spectrum of disease settings. I think that is through, as I mentioned in my earlier comments, this disease, this patient population are widely dispersed around the country, and in terms of their healthcare settings, whether it is academic centers, rural centers, and everything in between. There are some centers of excellence where many of them are relatively embryonic. Ultimately, the patients are out there seeing a large number of healthcare professionals. When you think about the 40,000 patient population, that population is seeing about 25,000 healthcare professionals in the given year. You can see that actually we do have to go out and educate a large number of physicians. Over time, as we increase that education and people get the experience of how to prescribe this drug, and they see the type of impact it has on their patients, that obviously encourages future prescribing, as well as peer-to-peer education, which is also incredibly important. Out of the 25,000 healthcare professional population that is looking after these patients, we now at the end of Q2, had around 5,000 of those healthcare professionals who have prescribed ARCALYST at any point over the last five years. Again, whether you look at the patient population or the prescriber population and how many have prescribed and how many are yet to be switched on, you can see that the opportunity ahead is pretty substantial. For those patients that are on the drug, they are clearly staying on the drug for a good period of time because it is working for them. Can you talk a little bit about the reasons why a patient tends to want to come off drug? I used to say, well, if this was maybe five, 10 years ago, I would say it is because it is an injectable, but clearly the world of GLP-1s has shown us that injectables are not that big of a deal, right? Just wanted to understand what is the drive there in coming off of it. It is just to see if potential disease has been eradicated or you are cured or. Yeah. John, maybe I could ask you to answer the question, but maybe I will just say that generally, as you have seen, duration of treatment of ARCALYST has been growing over time, updated in two years, around three years. Clearly patients are getting on well on therapy. The reports that we have from patients is that ARCALYST is very substantially helping them and their disease, and they are very satisfied with being on ARCALYST. The compliance rate is very good. The market access rate is very good, and year on year as well. I think all of those things are going very well. John, maybe you want to speak to when does a patient stop, and how do they know how to trial a stop and go onward to treatment if needed. Yeah, happy to go into that. Actually, extending a little bit from Ross' prior answer about the median duration of disease being about three years. What we know from the clinical trial experience is that while patients are on therapy, the IL-1 pathway is suppressed, and so thus disease activity is suppressed, and the patients do well. You know, what we also know, just from the history of the disease, regardless of what entity they're being treated with, whether it's IL-1 pathway inhibition, steroids, or anything else, if the underlying disease is still present and you withdraw therapy, then of course the underlying disease will in fact come back. What we learned from our own experience, for example, is for these patients who had multiple recurrences, who had been treated for up to three years in the clinical trials, even at that point, they still had extant disease, as evidenced by the fact that the disease came back when the drug was withheld in the trial setting. What's important to note is that it's a good barometer, meaning if the chest pain starts to return, it's not necessary to wait for a full-blown flare. In fact, we have information from the trials, which is also part of the patient education materials, is that with ARCALYST, there's enough drug on board that after the drug is stopped and there's, let's say, a trial of cessation to see if the underlying disease is still present, it takes about six weeks for the drug to wash off. Then there's about a two week prodrome while IL-1 pathway signaling resumes. What you see is a gradual increase in chest pain. So if patients and their physicians are attuned to that concept, they realize, okay, the underlying disease must be present because IL-1 pathway signaling has resumed, and so the drug can then be reinitiated. That was done in the clinical trials, and the disease is put back under control. They can stay on therapy, again, for an extended period of time until the patient and physician reach the decision to see if, at a later date, perhaps a year or 2 later, the disease may have resolved on its own. Because in that sense, that's the one piece that we don't fully understand, which is, what are the drivers of self-recognition and autoinflammation? We do have an understanding of those risk factors, so physicians and patients can go through those risk factors and reach a decision about how long they should treat for, what is the mechanism for assaying for underlying disease, and then, again, resuming treatment if additional treatment is needed. Great. I wanted to jump over to your pipeline now, because that's becoming a really important part of the focus of the story. KPL-387 is your follow on IL-1 blocker for recurrent pericarditis. It's the same target, but a different mechanism. Can you talk about how 387 is differentiated from ARCALYST, and if approved, how is that going to be positioned in relation to ARCALYST? Is this something we expect to supplant ARCALYST altogether, or is there room for both drugs? Yeah. I think at this time point, a lot of that is too early to say. It'll be data dependent. Obviously we're focusing on the data and the clinical trials very heavily right now. We started the phase III and enrolling dosing in the phase III, and we shared some of the phase II data a couple of weeks ago, which gave us the confidence of moving in with our target profile into the phase III. I think time will tell, Edward, but I think one of the things that we have learnt is that bringing additional treatment options to the market for recurrent pericarditis that are highly efficacious and well-tolerated could expand the total IL-1 inhibition market overall. We know this disease is mediated by IL-1 alpha and beta. Both of those two cytokines are incredibly important within the disease space. The market research that we had from physicians, if the KPL-387 target product profile is met and makes it to market, that the physicians, and indeed patients, believe that that would expand the utilization of IL-1 alpha and beta overall. I think the rest of it is obviously there's a lot of time to go for us to work through exactly what those details look like and when we have more insight into the data. Got it. Maybe could you talk just a little bit about the current phase II, III design? Sure. For operational efficiency, what we did was we combined the phase II and the phase III portions of the development program into a single program. The phase II program, as Ross mentioned, is a dose-focusing portion in order to help us affirm, if you will, that KPL-387 could in fact meet its target product profile of once-monthly dosing. Those are the data that we recently shared, which showed that rapid onset of action. Despite the monthly duration of action, it was rapid in its onset with time to treatment response, which is the primary efficacy endpoint of four days. That meant that the cadence and the magnitude of that onset of action is rapid. But also there's a durability of response which lasted throughout the dosing interval, which gives us a lot of confidence in going forward into phase III. What we've commented on is that that profile, if you will, in terms of the performance characteristics of KPL-387 are consistent with the clinical trials that we conducted with rilonacept that led to approval. Now, as Ross mentioned, we're in the phase III portion of the phase II/III study. It's called PASTEURAL, and that study is essentially a randomized withdrawal outcomes trial. That basically has a primary efficacy endpoint of time to first pericarditis recurrence and is designed to look at the reduction in risk of pericarditis recurrence when the drug is given long-term in a placebo-controlled setting. That study, we believe, is pivotal, and not only pivotal in nature, but can support our registration. We have other activities ongoing, another phase II study to help with dosing and administration, and some long-term extension. That's the totality of the package. It really focuses on the phase III PASTEURAL program. Just very quickly, I know we just have a few seconds left, but we saw Novo Nordisk just recently announce their phase III results from the ZEUS trial, their IL-6 antibody, and it did not show a clinical benefit on MACE. But we did see the expected reductions in IL-6 and C-reactive protein. Does this data have any implications at all with regards to a read-through into RP? A read-through into RP, not necessarily, but what it does do is it focuses attention back on the IL-1 mechanism. As you know, statins reduce risk by a third, and there's been focus on the inflammatory mechanism as another way of readdressing the residual risk. The CANTOS study, which was with canakinumab, that blocked IL-1 beta, did show reductions in cardiovascular risk. Then the question that the ZEUS trial, which is very well designed, was trying to look at was if IL-1, of course, sets off a cascade of different activities, one of which is the increase of IL-6, and IL-6 goes to the liver, and it's the liver that makes the increase in C-reactive protein. So it's not surprising that C-reactive protein went down. But what that does tell us is that in that space between IL-1 and IL-6, that appears to be where the inflammation related to cardiovascular disease and atherosclerosis, perhaps in the innate immune system, seems to be targeted. So I guess in that sense, what it does is it focuses attention back on the importance of the IL-1 mechanism in terms of innate immunity in atherosclerosis. Thank you very much. Well, you got a great management team, strong balance sheet, a really commercial product that's on fire right now and growing significantly, and a really strong pipeline. So great to have you guys here today to tell us about it. Thank you very much for your time. Thanks. Thank you. We've got lots of different.