Welcome to the second day of the Citi BioPharma Back to School Conference. This is our 20th annual. Last year we didn't do it, and we opted to put all the biotech companies in the Global Healthcare Conference in Miami. This year we're doing both, and hopefully you guys do both as well. Kiniksa is with us. We're thrilled to have Sanj Patel, CEO; Ross Moat, CCO, and John Paolini, Chief Medical Officer, CMO. Thanks guys for joining us. The usual, football, banter. I don't know, when's Liverpool going to lose a game? Never? Let's talk about ARCALYST. You guys, it's been a home run, you know, for you guys commercially. It's helped, you know, build the company, build commercial, build the R&D organization. I guess the bigger picture question is in the, in the RP, the recurrent pericarditis market. What's the, is there sort of a tipping point in terms of awareness, like patient advocacy? Like, I'm trying to think if you can prime the pump ahead of the next gen launches. Are there patients that are not, you know, that are diagnosed and maybe not willing to go on and they're waiting for kind of a next gen? Is that, is that a potential bigger picture right on the market? Before we get started, I will say that we will be making all of the mistakes today that I was hoping to risk facilitating, but it'll be a lot of things to come with this. The journey here in Ireland, we're incredibly excited about the commercialization of our software. It's only been a couple of more years, actually, since far, you know, I'm really, really getting to a greater traction in Ireland and what value we've certainly penetrated into that. Probably a little too great too great about. No, that's reported. We came to, we just highlighted that our ideal is to have six clinical providers to support $1 million for the year. As a fact, we just four years ago to really believe this. Thank you. We believe there is an awful lot of opportunity ahead of us with ARCALYST still to be gained. We're certainly continuing to execute, penetrate into the target patient population. Last reported, we said we're about 15% penetrated into the population. We say there's still an awful lot for us to do going forward. We've certainly got some great momentum. You've seen that from the growth we've had so far. We've steadily increased the sales force size, but importantly, we've focused on some of the key drivers like the duration of therapy. Compliance has been very strong, over 85%. Our payer approval rate has been very strong, over 90%. Most importantly, the blocking and tackling, and as you mentioned, the disease education has been very, very important. It's allowing us to have the growth rate that we've had so far. That said, we still believe there's a lot of opportunity. We are continuing to look at the different territories, how we split the territories. We're looking at potential overlays in our field force, territories. We think there's an awful lot more to be done. Despite that, as you mentioned, at some point there will be competition, I'm sure. We are the leader in the recurrent pericarditis space. We fully intend to continue to be the leader. We do have KPL-387, which is a very exciting development program that's now in a Phase II, Phase III study that we've worked with the FDA on, and that's potentially a monthly liquid formulation subcutaneous injection. Ross, I think we'll talk a little bit about some of the market research that we've just this morning described in our corporate presentation and provided in a SEC filing. There's an awful lot of opportunity ahead. Maybe Ross, you want to talk about some of the more tactical things that we're doing to make sure that we maintain that leadership position. Yeah. Thank you, Sanj. I hope you can hear me. Thank you for the summary and the overview. Just to echo, yes, we feel like we've made good progress, launch to date. Things have been growing nicely. In Q2, we had a strong quarter of $156.8 million in net revenue, which was a 52% year-over-year growth. We were pleased to increase our revenue guidance for the full year 2025 from $590 million- $605 million, up to $625 million- $640 million. I think the important thing is that while we're making good progress, we remain even more excited about the future. We're around 15% penetrated into the 2+ recurrence group, which is a 14,000 patient population that have suffered for two or more recurrences in any given year. That's not to mention those patients that are in the first recurrence group, which is still within label, the broad label that we have assigned by the FDA, just broadly for recurrent pericarditis. We're making inroads into that patient population as well on top of the 14,000. That's an additional 26,000 patients that are on their first recurrence, making 40,000 patients in totality. Now around 20% of all the patients that are prescribed ARCALYST are actually on their first recurrence. That's also been growing nicely. As Sanj mentioned, we're around 15% penetrated into that 14,000 group versus this time, or the same time last year, the end of Q2, that was 11%. That's been growing reasonably well. We have a huge opportunity ahead to continue to grow ARCALYST, continue to switch on more and more prescribers. As you know, this is a patient population that's quite widely dispersed, and maybe later we go into the more recent advent of pericardial disease centers and kind of what's happening to that treatment landscape. The patient population is very broad, seeing any one of the 30,000 or so cardiologists and rheumatologists around the country. In Q2, we had one of the highest growths we've ever had in terms of new patient enrollments, but also the number of prescribers. We had more than 300 additional total prescribers, new prescribers coming in. That's taken the total prescriber count to just more than 3,475. Around 27% or 940 of those are written for two or more patients. Continuing to make sure that those prescribers, as well as new ones coming into the mix, have a positive prescribing experience is incredibly important. That means that they know how to identify the patients, how to separate, you know, recurrent pericarditis patients from those that are just suffering the first index episode of pericarditis, and to treat it as a distinct disease, acknowledging that it's an interleukin-1α/β–mediated disease, and the growing literature has been supporting that. As people become more and more comfortable with prescribing it, knowing how to prescribe it, going through the prior authorization, seeing their patients get onto therapy, of which we have an incredibly high payer approval rate, and seeing how their patients do on therapy, all goes into the good experience that encourages them, one, to share with other physicians, but also to identify and prescribe for more patients. Maybe I'll stop there, Jeff, and I'm happy to go in any other direction. Can I follow up on that? You have a drug that's over $600 million. You have only 15%- 20% penetration depending on the denominator. I mean, you have a lot of headspace. I guess that's the obvious question: why is that not 50%? If this was such an urgent disease, does it mean that there are logistical challenges in onboarding patients, on identification, reimbursement? Or does it mean that there are therapies out there that patients are pretty comfortable with and they have to get to more recurrence before they're comfortable onboarding? Does that make sense? Yeah, it does, Jeff. This is one of the challenges of the marketplace that we've been addressing since launch and continue to do so, where this is the fact of a rare and flaring disease and a disease which is very widely spread across the U.S. in terms of not having historically kind of centers of excellence looking after these patients. Unlike in some other rare diseases, particularly genetic diseases and so on, where all patients are identified or looked after by key centers, that's just not the case in recurrent pericarditis. The other factors, I think, are the fact that this is a disease which physicians have historically reached for something like a corticosteroid to try to control the disease, which can have a pretty significant impact on inflammation pretty quickly and maybe make the patient feel better. Although, I think the growing wealth of evidence is that there's probably not the most modern approach or the right approach to treating this patient population, understanding that it's an interleukin-1α/β–mediated disease mediated disease. In fact, we've started to see many more publications now, most recently, I think, with the ACC Concise Clinical Guidance publication just in the last prior weeks, acknowledging that interleukin-1α/β should be utilized ahead of corticosteroids for patients that have recurrent pericarditis, patients with this autoinflammatory phenotype. This is really publications that are starting to come into play and change the treatment landscape, which are very much aligned with how we've been promoting and trying to educate on recurrent pericarditis and ARCALYST over time. It takes time, given that it's a rare flaring disease and the whole landscape is changing and patients are widely spread. Would you say now that you're, you know, over $600 million in revenue, you probably have popped on the radar, right, of, I don't know, payers, just given the magnitude of the opportunity. Obviously, I'm sure Regeneron is kind of like, we didn't think this would be this big of a drug and had this kind of growth. Does that add any additional sort of risks to you guys from a reimbursement or from maybe a positioning standpoint within the standard of care for RP? I mean, most importantly, we have a phenomenal data set primarily from the RHAPSODY study, the pivotal trial that we use. That data set is obviously a very, very important tool as we talk to payers. As we talked about earlier on, the payer approval rate continues to be very high, over 90% since launch. I think at the end of the day, when you're talking about value-based medicines and you've got a drug like ARCALYST, which has the evidence that it has, we really haven't seen the barriers that you've been talking about. That doesn't mean that we don't do an awful lot of work to educate physicians as well as payers in terms of the evidence that we have so far. That's a constant effort. We have a very strong payer group that works with those people. It's a matter of just continuing to explain that, in addition to the pivotal study, we've had great data from the registry as well as the long-term extension studies, which only continues to bolster the benefits of ARCALYST. That's been our real key effort for us internally, but it's worked very well and continues to do. Yeah, and maybe just to add, I mean, the payer landscape has continued to, I think, reflect the value that this drug brings to these patients that are suffering from a very debilitating disease, which dramatically affects their quality of life. It's really reflected, I think, the more modern way of treating the disease, which I think goes to your prior question a little bit as well. In terms of the costs to patients, I think it's worthwhile noting that eligible commercial patients generally have a zero copay, where we're able to buy down the copay to remove that kind of access or copay barrier, if you like. I think that goes back a little bit to your last question in terms of, you know, some physicians believe that this can be an expensive therapy, that patients may not get onto therapy, that it's going to cost too much. They haven't had, cardiologists in particular, have not had the best prior experience with biologic prescribing, particularly around PCSK9 inhibitors, which are a much larger patient population with many payer barriers historically that have been in place. I think there's a little bit of a legacy effect from that. As physicians start prescribing for ARCALYST and they see that the payers approve it, that patients get onto therapy, the copays are very low, if anything, for eligible patients. With the Medicare Part D patients and the IRA changes, there's caps on co-payments and so on. Patients are generally getting onto therapy pretty easily. We're pleased with what the payer landscape looks like and how it reflects the value that ARCALYST brings to these patients. Of course, it's always a changing environment. It's something that we keep an eye on and we continue to have those payer conversations to try to make sure that they really do see this as the way for treating the disease for the future. Makes sense. Let's talk a little bit about KPL-387. Maybe to start, just give us the context or history here. Was this something that was strategically important to you guys to have a longer-acting, less frequent dosing interval? When you thought about what you could add to the ARCALYST clinical profile, in terms of maybe higher efficacy, better tolerability, it seems to be a pretty good drug on its own. What do you think you could add to even further differentiate, sort of aspirationally, when you look to the phase two, three? Yeah, I mean, you know, obviously, as I said, we are the leaders in recurrent pericarditis, and it's important that we felt it's important that we remain that way. Obviously, as we've said, we still believe there's an awful lot of room to grow with ARCALYST, but having potentially a monthly liquid formulation subcutaneous injection, I think, you know, would be beneficial. Ross can talk a little bit about the market research that we just put out this morning, which shows you that there's significant interest potentially in patients for that treatment modality. I'm sure there'll be some patients that prefer to stay on ARCALYST as well, but providing that potential treatment option, we felt was very, very important. Obviously, the data remains to be seen from the phase II and phase III study. We'll have data in the second half of next year from the phase two, dose focusing portion, and we intend to be in the market with KPL-387 in the 2028-2029 timeframe. Maybe Ross, you can talk about the market research done so far, and then John, just a little bit about the clinical trial and what we hope to see there. Yeah, happy to do so. Thank you. We did update the corporate deck, the corporate investor deck this morning with a slide around market research that we've recently been working on and interviewing both patients and healthcare professionals with the target product profile of KPL-387, which is being a highly efficacious interleukin-1α/β inhibitor with a potential monthly treatment paradigm in potentially an auto injector. I think those results are quite compelling. We feel that the opportunity left for ARCALYST is significant, and we are very focused on making sure we continue to help patients with ARCALYST, continue to grow ARCALYST. Of course, we're a company that focuses on execution, but we're also a company that focuses on innovation and providing greater value for the future for patients and all stakeholders. We were pleased with the target product profile market research results that we had out, which was ultimately showing that physicians believe that an introduction of KPL-387 to the market would expand the interleukin-1α/β market overall. When you break it down via patients and healthcare professionals, around 75% of the patients said that they would prefer the target product profile of KPL-387 if indeed that comes through to fruition through our clinical trials. 70% of the patients said that KPL-387 would likely draw them towards a longer duration and better compliance rates as well. We're happy with the compliance rates and the duration has been growing with ARCALYST; they felt that a monthly version in an auto injector would help to enable that for the future, longer duration, better compliance, and fewer missed doses. On the healthcare professional side, around 92% of the healthcare professionals stated that they are highly likely to prescribe KPL-387 if it were to come to the market for their new recurrent pericarditis patients, as well as acknowledging that existing patients that are treated could potentially be transitioned to KPL-387 if patients desired that or came in to request a change to a different target product profile. Maybe on that note, it may be helpful to pass over to John to talk around the clinical work that we're doing to support that when we come to launch. Sure. Yeah, happy to do that. Yeah, we're very excited about the KPL-387 program. It's obviously a very comprehensive package of data that we're putting together for a novel asset. We're working our way through the phase one program now, which is coming to an end, which has already shown, actually for quite some time now, we presented data that supported that single injection, subcutaneously, of KPL-387 stays above the target concentration for 57 days. This supports the concept of once monthly dosing. Of course, it's a liquid formulation, so that enabled us to move forward into the phase two/three clinical trial, which is kind of the centerpiece, if you will, of the development program. What we're working through right now, we've talked about the fact that we've initiated the dose focusing portion of the trial, and that's really to confirm the dose level that we're taking forward into the pivotal trial. We've talked about the fact that those data would be available. We anticipate them in the second half of 2026. The centerpiece, from a pivotal perspective, is the phase three portion of that trial. Of course, that's the randomized withdrawal trial that provides the critical evidence of efficacy and safety to support registrations to pivotal data set. In addition, we have a dosing and administration clinical trial that's also on the development package that we've outlined in our disclosures today, which basically covers some of the important information about the transition to KPL-387 monotherapy from patients who are on existing therapies. That supplemental data really rounds out the package. The final set, of course, are all the long-term extensions that provide long-term efficacy and safety data since, as a new compound in the market, and especially, as Ross mentioned, the importance of aligning the treatment interval and the duration of treatment to the duration of the disease, which, as you know, is a median of three years, that long-term extension information is designed to provide important safety information over that kind of a duration of treatment. We're excited about the program, and we're happy to talk more about any of those details. Yeah, I guess looking at the update expected next year, how should we frame the phase two update in terms of what would be clinically meaningful for patients, given that you do have ARCALYST on the market now, I guess, in terms of safety or efficacy? Right. Yeah, as Sanj said, we've been the leaders in this space and leading with regard to bringing forward to patients definitive therapy for recurrent pericarditis. That's based upon the fact that blockade of the IL-1α and IL-1β cytokines, and thus complete abrogation of the IL-1 signaling pathway, is aligned with very powerful efficacy for patients. That, in a sense, can set the bar of how patients can do when you give them highly effective therapy. We're obviously very much aware of that. The trial that we've set up enables us to understand the PK/PD relationship of KPL-387 in clinical practice in patients with recurrent pericarditis. That's why we are studying four different dose levels in this study. We have a very firm understanding going into the study in terms of the monthly dosing pharmacokinetics at one particular dose level of 300 mg every four weeks. The idea is to look above that and to see whether more drug imparts more efficacy or not, as well as to show that giving less drug or less frequent drug uncovers some of the elements of the PK/PD relationship that allow us to focus in on the critical dose level that we bring forward. At this point, we anticipate that being the monthly dose. What that allows us to do in the phase two study is to look for onset of action, which is the primary efficacy endpoint, as well as to look at, as the drug is dosed at intervals over the six-month period of time, and we look at peaks and troughs, we can understand how the inflammatory response takes place or doesn't during those dosing intervals. That's the critical information that we'll get from that study. It's really more around how the drug works in patients, initial safety data. Of course, the pivotal trial is the trial that's designed to show the kind of data that supports the registration package. Great, thank you. I guess looking at the KPL-387 market as a whole, are you looking at, similarly with ARCALYST, how you jump into both the first and multiple recurrences? Is that something that you're seeing here, or are you looking to kind of have a different market? Yeah, so, you know, the way the trials are designed, you know, we've come a long way in the last 10 years. RHAPSODY was designed to, you know, to look at the recurrent pericarditis population, which at that time was heavily influenced by third-line use of drug, meaning after steroids. That kind of broke with that paradigm and established a new paradigm of treating a second line, meaning ahead of corticosteroids and after NSAIDs and colchicine failures. What I, you know, there are elements of the, and what we want with our KPL-387 program is to be, you know, provide critical data to support registration, but also to think about the practice of cardiology and the practice of managing recurrent pericarditis for the next 10 years or 15 years or 20 years, and to establish that evidentiary base to move the field forward. We've disclosed certain elements of the program that you've seen so far. There are other elements of the program that we haven't discussed, but suffice it to say, the idea of supporting not only third line, but also importantly centering on second line use, since that's the treatment paradigm in the U.S., is of critical importance. It's also important to know that sometimes the requirement of two or more recurrences that you often see in a clinical trial, that's not because of the biology per se of the disease or that treating earlier in the disease, IL-1 pathway inhibition would not work. The reason why we do that is mostly around the study endpoints to make sure that recurrences, when they take place in the clinical trial, are robust and brisk, and therefore it provides a good measure for the efficacy of the drug. What we've seen in the real world is that actually, regardless of where you are in your disease course in terms of a line of therapy or number of recurrences, we see powerful efficacy. In fact, we just showed data at the European Society of Cardiology meetings a couple of days ago, data from the residents' registry. What the residents' registry showed was that as you looked at patients who were starting ARCALYST, or IL-1 pathway inhibition at large, but across any line of therapy, if you look at what their life was like before they started that, it was on average four recurrences per year, which is an awful thing when you think about that. When you look at how they did after ARCALYST initiation, it was 0.02 events per patient year. That is a 99.5% reduction in pericarditis risk after versus before. That is regardless of line of therapy. I think the kind of data set that we're generating as leaders in this space, we hope will bring the best therapy to patients at the right time. Great. Could you talk a little bit more about the opportunity for switching from ARCALYST to KPL-387, if approved? Maybe how are you looking at balancing bringing on switch patients versus new patient starts? Yeah, happy to go through that. Thank you for the question. I think that's, that's in part, you know, a key part of why we announced the study that we're doing this morning, which is the transition to KPL-387 monotherapy. At the time of launch, there's data in hand to guide physicians if indeed that's what they want to do with their patients of moving people from, you know, an interleukin-1 alpha-beta inhibition to another drug, which they may deem as, as, you know, better for the patients to be on. That data hopefully will be in hand by the time of launch. As John said, that's kind of a supplementary, rather than part of the necessary regulatory pathway, which is the Phase III pivotal study. We think that's important, but ultimately it's going to be, you know, physician and patients' experience and desire of what they want to try to manage this disease. We remain very optimistic about ARCALYST. It's making great waves in the recurrent pericarditis market. It's helping thousands of patients, and we believe that there's a massive opportunity ahead to still continue to grow ARCALYST. That's going to be our focus. If and when we get to a launch of KPL-387, the data will be there to guide people on how to transition if indeed it's what they want to do. What we hear from both patients and healthcare professionals in the market research that we announced this morning is that they reacted very well to the target product profile of KPL-387, that they deemed that as a good product profile to prescribe, ahead of other therapies for both whether it's commercially available therapies or other therapies that are in the clinical realm that are known about now, for new patients, or if they want to transition patients, particularly if the patients request a change, then physicians were very willing to take that on board. Great. I guess looking a little bit more into the ARCALYST market itself, you guys gave a great overview already, but just to dial in a little bit more, could you talk a little bit about the growth in new versus repeat prescribers? I guess could you talk about your strategy there? Yeah, I'm certainly happy to. It has been growing very well, both new and repeat prescribers. As I say, in Q2, it was one of the highest growths that we've ever seen of more than 300 new physicians coming in and prescribing ARCALYST for the first time, which, you know, are four and a bit years out from the launch, shows that up until the end of Q3, at least, there were no signs of slowing down, and the opportunity is still very much there for future growth. I think the penetration numbers tell you the same thing as well as the prescriber numbers, so we're pretty pleased about that. 27% of those have prescribed for two or more patients, and they're getting good experiences, so we think that's very important and kind of bodes well for the future. Just to tie it all together, I guess the question is, does the commercial success with ARCALYST or the potential profile with KPL-387, does that change how you're thinking strategically about the OUS market, in terms of the cadence of investments and launch and sort of build out, et cetera? Yeah, I think obviously a lot will be data-driven, as we continue to progress the 387 study. Certainly the clinical trial is a very global, you know, focused study. Certainly, as always, we continue to look at value-creating opportunities, certainly when it comes to commercialization. We look very closely at outside U.S. opportunities as we've done historically. Yeah, again, but data-driven. Okay. With 387, given the mechanism, I wasn't sure if the related adjacent sort of rare indications outside of recurrent pericarditis could be in play. Have you guys explored that at all, like in preclinical or sort of mechanism type of studies? Yeah, I mean, certainly we're very interested in a number of different areas outside of recurrent pericarditis. We have looked at other rare specialty cardiovascular diseases. Certainly, we believe that focusing on IL-1 is very important. IL-1 mediated disease is very, very important, where both a monthly and potentially even a quarterly drug like our 1161 program could be potentially very useful. We'll continue that work, and when it's the right time, we'll disclose where we're focusing 1161. We are looking at a number of different indications across both those programs. Okay. Yeah. While we're on 1161, I think when you look at a lot of the innovations in gene and cell therapy with sort of curative intent, much longer dosing intervals or disease sort of free kind of intervals. Is that a risk to you guys when you think about, not necessarily cell therapy, but maybe a super long-acting like engineered antibodies that have half a year or annual dosing, something like that? Is that potentially in the works with 1161? Could you engineer that for even further? Are there other kind of longer acting? Does the disease work? Some indications don't work to have that. Yes, it certainly is disease-specific, indication-specific without doubt. No, I don't know. I don't see it as a risk. I see it as an opportunity for us to innovate. That's where 387 came about, and that's how 1161 came about. For us, we don't see these as a risk as much as we see these as opportunities for us to maintain being a leader in any particular therapeutic area. For us, we are certainly, you know, we do have our own lab in Lexington, MA, as well as a manufacturing facility, up to Phase 2. We continue to look at areas that we can create value, help patients, and, you know, whether they're longer-acting therapies or whether they're shorter, it all depends on the disease that we're focused on and on the unmet need. Certainly very excited to see some of the data from these longer, you know, technologies that are there. There's been sort of ups and downs, as you can see, in sort of safety and efficacy. Certainly for us, we hope that they do well and hope that we continue to innovate. I don't know, John, if you want anything to add on. Yeah. Maybe more bigger picture signs, when you think about the financial performance, the top line ARCALYST growth has been fantastic and continued execution. You guys have been profitable and cash flow breakeven. I know you're committed to being cash flow positive, but not quite bottom line. I guess the question is, to what degree do you think that BD or portfolio diversification is going to be a more impactful or play a bigger role? Do you think just delivering on good bottom line performance will sort of outweigh in terms of the priorities? Yeah, I mean, as we're going high level, I'll tell you that we're a group that's incredibly focused on value creation. We're a group that never gets complacent. On the one hand, you say we're profitable and cash flow positive. For us, hopefully what we do in the future dwarfs what we're doing now. That does come from innovation, and it may also come from business development. We are looking at a range of opportunities. We've always from day one focused on capital allocation. For us to make any investment, we better be pretty darn sure that it's going to create value, you know, for the shareholders, for patients. There's an awful lot of opportunity ahead of us, and certainly the fact that we're in a great cash position, cash flow is obviously a very strong part of the story, just gives us really nice options to look into opportunities. Our bar remains incredibly high and rest assured we never get complacent. For us, we see this as only the beginning. Obviously we've talked about future growth at ARCALYST. We've talked about launching KPL-387 and KPL-1161. For us, BD is only another part of that solid stool, that leg of that stool that we've got to continue to focus on. It's how we built the company, and I'm sure it's how we'll create further value in the future. I think when you look at the playbook, you know, in orphan, the U.S. and Europe are the more well-established, Japan regular way markets, and there's probably plenty of patients there. Is there a chance if you have the profile that you really want for 387 or 1161, is there a partnering opportunity for other geographies that may not be worth you building out sales and marketing and infrastructure? I mean, that's certainly a possibility. You know, we've shown that we can partner very well. We've done that with Vixarelimab, as you know, with Roche, and that was an incredibly strong deal for Kiniksa, and I think obviously for Roche as well. At the same time, we've also shown that we can commercialize drugs exceedingly well. We've got to look at both what we could do potentially ourselves versus what a partner could do in, as you say, certain regions or certain indications. We look at those things consistently, and we don't get wedded to anything. For us, it's about where can we create the most value and be incredibly discerning when it comes to that. Yeah, we're very excited, but we'll certainly look at all those options to create the most value possible. Yeah. Are there pockets outside, like on a global basis at the disease epidemiology? Are there countries that maybe you are not, you know, not as well appreciated that you have a higher rate of RP or, you know, like high incidence rates or diagnosis rates, higher awareness, you know? No, nothing really to note there, Jeff, no. Okay. All right. Awesome. Thanks, guys. Appreciate your time. Thank you. Thank you very much. Thank you very much. Thank you.