My name's Geoff Meacham. I'm a senior biopharma analyst here, and we're thrilled today to have the Kiniksa team with us. So speaking on behalf of Kiniksa, we have CEO Sanj Patel, Head of Commercial Ross Moat, and then John Paolini, Chief Medical Officer. Guys, thanks for coming. Good to see you. Thanks for having us. Yeah. So, Sanj, I guess just for the folks that aren't as familiar with the story, just give us kind of the quick elevator pitch, and we'll get to some questions. Probably spend a little bit of time on ARCALYST. Yeah, happy to do it. So, obviously, first of all, as usual, please know I will be making forward-looking statements today that are subject to risk and uncertainties. You can refer to those in the SEC filings. So happy to be here. Kiniksa is very much a growth-oriented, well-capitalized company. Company was formed just around 8 years ago, and since that time, as Geoff knows well, we've collated some very interesting and compelling assets. We are now a commercial company and, in fact, cash flow positive on an annual basis. The launch of ARCALYST just now, three years since launch, has gone incredibly well. In fact, we've just announced that in our first quarter, we had a quarter of $78.9 million for the quarter and, in fact, increased our guidance for the year to $370 million-$390 million. That, at the midpoint, represents roughly 63% year-over-year growth since the last year. So obviously, incredibly pleased with the commercial execution with ARCALYST. We intend to continue that growth and continue to nail it commercially. But on top of that, we're also looking at growth, obviously, from the rest of the pipeline. We have announced that we're moving our abiprubart molecule, which is a CD40/CD154 molecule, into phase II. We're going to be starting a Sjögren’s study in the second half of this year. That's on the heels now of positive data in terms of proof of concept that we had in our RA. And obviously, very keen to see how that molecule moves forward. A lot of external proof of concept for interrupting the CD40/CD154 mechanism. So exciting movements there. As Geoff knows, we are always keen to do business development, both for the in- licensing on the outlicensing side. We've had some successful deals done with vixarelimab, which was an IL-31 oncostatin M molecule that we outlicensed to Roche/Genentech. And that was for around $125 million plus royalties and milestones. And so obviously, we're looking forward to that. And we are looking to monetize our mavrilimumab molecule. This is an anti-GM-CSF molecule that we took through phase II in a number of positive indications. So a lot going on with the company. Needless to say, execution both on the commercial front and on the clinical development front is top of mind. Yep. Yeah, so let's talk a little bit about ARCALYST and the, the sort of the recent commercial dynamics. You know, would you say Sanj and maybe Ross too, looking forward, what's the has it been the primary driver? Is it persistent rates of patients? That seems to be growing, you know, quite nicely. Is it, you know, the awareness and finding patients? I'm sure that it's probably all the above, but what would you characterize kind of as the bigger driver of late? Yeah, maybe I'll start, Ross, and then feel free to jump in. I mean, I think, again, it's all about penetration. So we've often said that there's around 14,000 patients in the U.S. that suffer from two or more recurrences. And those have been the sort of target patient population that we've been focused on penetrating into. Last reported, we said we penetrated around 9% into that 14,000. On the one hand, it tells you they've got a lot more work to do. It also tells you there's a lot more opportunity. So really, it's all of the things that you mentioned. I mean, certainly, duration of therapy is very important. Last reported, we said that the duration's roughly around 23 months. When we first launched in April of 2021, we figured it maybe be around 6-9 months. That increased to 9-12 months. And then prior penultimately was around 18 months. So that duration certainly helped. But on top of that, it seems like educating the physicians. We've now got around 2,000 prescribers, that we've recently announced, and that and 24% of those are repeat prescribers. So it's really educating you on not just duration but also the importance of compliance. We've got a very high approval rate within the payer network, and so we're working very hard. That's been around 90% quarter-over-quarter. So those all go towards that increasing growth. And And certainly, our expectations for the future, I'm sure Ross will cover the recently expanded sales force to around 85. Yep. Sales reps, up from around 50. That's quite nascent. That happened at the end of last year. Hopefully, in the middle of this year, we'll see that really come to fruition. So Ross, anything to add? No, I think that's all great and well summarized. I guess the only thing I would add is that we're just very focused on the awareness of recurrent pericarditis, how to distinguish recurrent pericarditis from an initial, acute pericarditis or the index episode of pericarditis. So patients get diagnosed accurately and quickly and treated early. So we focus on that very much, with our field team execution, and other kind of awareness activities that we have around ARCALYST and around recurrent pericarditis. So that's key to us. And we're seeing the awareness grow substantially, since the time of our launch, year-over-year, and quarter-over-quarter. The awareness, the knowledge around ARCALYST has grown significantly, as Sanj outlined. The number of prescribers has grown pretty rapidly. And in fact, in the last quarter, Q1 versus Q4, we had the biggest growth in prescriber base that we've had so far since launch. So I think all that indicates that the awareness and knowledge is growing. And we are very focused on making sure that when physicians identify an appropriate patient and prescribe ARCALYST, that they have a good prescribing experience. They know how to prescribe the drug, how to get it reimbursed, how to go through the approval process, and to start their patients off and hopefully hear great feedback from their patients on how they feel once they're initiated on ARCALYST. And if we do all that well and help physicians and help patients, that will encourage them to identify and prescribe for more patients down the line. I guess the question is, is there a way to leverage the experience even further to, you know, not just enhance kind of the risk benefit but the cost benefit? In other words, can you follow patients and sort of present new data on longer-term follow-up and see the resulting, you know, kind of benefit on the cost side as well as obviously the clinical side? Yeah. I mean, John, maybe you can talk about the long-term extension of the data we've seen there. And obviously, what we're trying to obviously move forward in terms of publications as well. But there's an awful lot of education around the long-term extension data, the RESONANCE registry, which I think is a very important part of the education piece. Sure. Yeah, happy to cover that. Yeah, so in the main RHAPSODY study, which was the pivotal study that supported registration, the median duration of treatment was 9 months. And so that showed a 96% reduction in risk of pericarditis recurrence. What we showed in the long-term extension is then following those patients for further. And so in fact, at 18 months of treatment, then there was a trial of suspension of therapy. And what it showed was that there was a 75% recurrence rate in those that suspended therapy versus those that continued therapy. So that was a 98% relative risk reduction. It was consistent with the primary endpoint. What that showed is that the disease duration is long, and so therefore, if premature cessation of therapy unmasks the underlying disease process and leads to recurrence of disease. But the good news there is that while you see that recurrence and it tells you the disease is present, you can reinitiate therapy, and that brings the disease back under control. And so that becomes a core of the educational piece, which is to treat to the duration of the disease, which, you know, as Ross has mentioned in the past, you know, can be for those with multiple recurrent 2 or more recurrences be like 3 years. And so that's kind of the focus of the educational piece. Gotcha. Yeah, and then, I guess last question on the payer dynamics. You know, Sanj, you mentioned, you know, more and more, you know, wins and towards a sort of a more accelerated time on patient sort of onboarding. Help us with kind of what are the gaps still to fill yet on the payer side and maybe how the step edits with, you know, sort of frontline therapies have sort of evolved over time? Yeah, I mean, maybe I'll add some comments. And Ross, feel free to jump in. We haven't seen that much pushback, to be honest with you. Not to say that in any ways we're complacent. I think half the reason why we have such a high rate of compliance from the payer side or the reimbursement side is that we have proactively reached out. You have to remember, ARCALYST was an approved therapy. Yep. Prior to recurrent pericarditis, albeit for CAPS and now for DIRA, incredibly rare syndromes. But I think that has sort of helped people understand. But the data that John described, RHAPSODY, has really phenomenal data from the phase III pivotal study, 96% reduction, the p-values that were very strong, I think has helped us educate not just the physicians but also the payers in terms of the value that this therapy brings. And so we haven't had to date, again, not being complacent, a lot of pushback at all from the payers on the therapy. Ross, anything to add? Absolutely, right. We're very pleased with the payer approval rate. I mean, it's more than 90% in all completed cases. That's been the case, in fact, every single quarter since launch. So I think we've got a very strong value proposition and a robust value proposition that's understood well by payers. So we don't suffer from many payer edits, step edits, and that type of thing. There are some, you know, very small plans that may have something like corticosteroid use prior to ARCALYST. But all of our education is really on using ARCALYST as a steroid-sparing agent before corticosteroid use. And I think that's resonating very well with payers and is well understood. People understand that using corticosteroids can prolong the disease, and certainly the toxicity effects of patients being on those therapies can be pretty substantial. By the time patients are suffering from multiple recurrences, it's very clear that previous therapies have not worked in addressing the root cause of the disease. We know that the root cause is interleukin-1 alpha and beta. Providing a targeted therapy to help those patients manage the disease is incredibly important. I think we're seeing that live out in the payer world. And you guys' commercial success, you know, has mostly been U.S. Maybe just give us at a high level kind of your thoughts as this opportunity could evolve outside of that. Yeah, I mean, we are looking at it very carefully. We do have orphan drug designation in both the U.S. and Europe. Yep. and obviously, both Ross and I, having European background or a British background, we're very keen to understand the opportunity, ex-US, without a doubt. So we're looking at that very carefully. At this point, we have not disclosed our plans. But needless to say, it's not lost on us that there is other potential outside of the US. And, and that would obviously include potentially Europe given the orphan drug status. Is that a pretty significant, you know, financial investment to raise awareness and build the brand? Or is there an opportunity maybe to, you know, to use, you know, to partner up with somebody? Yeah, I mean, I think we'll look at both. I mean, we obviously, Ross and I in particular, have got a lot of experience working in Europe and launching drugs in Europe. You know, you can always have a very targeted launch as well. Yep. We're obviously thinking very carefully about how much investments you make upfront so you're not going all out. But as you say, we're obviously open to partnerships as well. We do have an existing partnership agreement with Huadong Medicine, which is a very large, Asian pharmaceutical company. And that's for the rights for ARCALYST and mavrilimumab, actually, across the Asia-Pacific region, excluding Japan. So obviously, that's another way that we could potentially help monetize the asset in other regions. So we certainly are potentially looking at ex-US and certainly keeping the optionality for other regions. Okay. Makes sense. And then I guess the last question is, you know, as you think about, you know, the, it's come up in a lot of other, you know, non-orphaned indications, but manufacturing capacity and things of that nature, right? So, are there any, you know, investments to be made, there with respect to, you know, supply? Or are you guys pretty much free and clear from that? You know, has there been any issues thus far? But is that something that you think about down the road when you, you know, expand? Yeah, I mean, we're always looking at expansion and always making sure that we have the supply. I mean, right now, obviously, as you're aware, Regeneron are manufacturing the drug. They've done that for years when they were supplying for CAPS. I mean, that continues. We have publicly stated that there is a tech transfer in process. Yep. That'll be in place with us. But again, it's something we're very much looking forward to. You know, whilst there has been a very strong partnership and there's been no issues to date, certainly it's nice to be able to control your own destiny. Yep. As we hopefully have, well, significant continued growth ahead of us, we're going to hopefully look forward to controlling that. Yep. Okay. Makes sense. Well, let's switch gears to 404. So maybe for those in the audience, just give us a little bit of a background for the, you know, CD40 antagonism and how, you know, that could really resonate right with the profile. Do you want to start? Sure. Yeah. So, the CD40/CD154 interaction really sits at the center of many immune-mediated diseases. So basically, CD40 is a cell surface molecule that's on the surface of B cells and antigen-presenting cells, CD154 on T cells and other cells. And it's an important co-stimulatory signal as antigens are presented or B cells or T cells are activated, that it kind of drives that activation process. And so, it's an attractive target to interrupt that co-stimulation as a way of blocking autoimmune diseases. And so there's a lot of external proof of concept about targeting either side of that interaction as a way of blocking autoimmune diseases. So, we're particularly excited about abiprubart because, as a CD40 antagonist, it has many properties that are very attractive: stable pharmacokinetics. We have a high concentration liquid formulation that's enabling subcutaneous dosing. And so, you know, we're moving that program forward, and we can, you know, talk about it as, as you'd like. Yeah, and, and I guess Sjögren's, talk a little bit about, you know, how you select the, you know, the indications that, you know, you, you, you could allocate capital towards it that you would prioritize. I know obviously, there's a science piece of it, but there's also, you know, a bit of a, you know, economics of it too. Sure. So maybe initially just, you know, the reason for initially studying rheumatoid arthritis with abiprubart was a way of establishing PK/PD relationships. Yep. So it's a large population of patients where there were very defined endpoints, a defined dose-response relationship. And so it enabled us to make the transition out of phase I to test subcutaneous dosing and establish the fact that we have a parity or similarity of response with weekly, biweekly, and monthly dosing. So that was a great place to start to give us a good benchmark, you know, with the asset. But then moving forward and thinking about, you know, further development, Sjögren's disease is a very important place for us to go. It's obviously a disease that is a devastating disease for those patients, you know, who have it. There are no approved therapies. And to us, as we thought about it, there it's the disease has been fundamentally de-risked because of the fact that, you know, there's been a lot of proof of concept external proof of concept work on both blocking CD40 as well as blocking CD154. However, when we think about the assets that have demonstrated that initial proof of concept, we believe that there's an opportunity for abiprubart to show differentiation advantage over those other assets. And so that allows us to move into that space, bolstered by the information that we've learned from our own phase II experience to go into the phase II trial that Sanj mentioned is anticipated to start in the second half of this year. And there we're testing biweekly and monthly dosing over a six-month period of time with then in a long-term extension to allow full treatment, you know, for the full, for the full year. And I think that will give us a lot of dose-focusing information on the drug, but then importantly, though, establishes, you know, really puts a flag in the ground, if you will, in a critically important autoimmune disease. I think it's also important to mention. I'm not sure if you did, but the potential for sub-Q dosing, I think, is also a potential real differentiator aside from the fact that you we are looking to study both biweekly and monthly. So the dosing modality as well as the route of administration, I think, could be an important differentiator, obviously, pending results. But did you guys intend to go into RA? Or, I mean, John, you mentioned that being sort of the proof of concept, you know, sort of for the molecule and the mechanism, right? But is there an idea that that could down the road be an indication? I mean. That's not trivial in terms of expense. Yeah, I'm sure, John, you can comment. But we did see some very compelling RF, rheumatoid factor data, very important pharmacodynamic marker in our phase II study with RA. And that was very compelling. And I think certainly, obviously, it's a large indication, as you say. We're not excluding the fact that we could consider partnering that. Yep. As you said earlier, but the data was compelling in many ways, certainly as far as RF factor was concerned. But also, let's also admit that, that safety was also very compelling as well in terms of the CD40 molecule. So we're pretty pleased with that. That's right. Sjögren's being, you know, a very much an unmet need. How would you characterize, you know, the mechanism versus other, you know, other things in the clinic? There's a ton of sort of retrofitted, you know, you know, anti you know, I mean, everything from TNFs to IL-13s. I mean, that have looked at maybe not as successfully, right? But help us with kind of how you view, you know, CD40 as, you know, as maybe a key player in Sjögren's. Right. Well, certainly, you know, because of the fact that it's a high unmet medical need, there have been a lot of efforts, you know, to try different types of immune modulation. Yep. In that disease space. Unfortunately for the patients, a lot of those have been unsuccessful. But when we think about this particular mechanism and why we're, you know, really enthusiastic about it, if you will, is because of the fact that when you think about the mechanism of disease, it really is ideally suited for this type of pathway inhibition. You know, antigen presentation, T- cell activation, B- cell activation. It's a multi-cell response, if you will. And so this particular pathway really sits, you know, right at the center. And the fact that there is already external proof of concept that, you know, provides that validation of the magnitude of the treatment effect that, you know, one can hope to see, certainly, you know, gives this mechanism a lot of promise. There are some other, you know, mechanisms that are in development that have also shown, you know, some, you know, some data. You know, that's, that's also good for patients that there are, you know, different options because of the way that this disease presents. But I think, importantly, the size of the population is also large enough, and there's enough disease heterogeneity, that it is a space that could support, you know, multiple assets in the space as clinicians make their choice about what's, you know, right for their patients. Similar to ARCALYST, right? I mean, you need to raise awareness first, right? But it all starts with having an effective drug. Right. And beyond Sjögren's, so, you know, I, I know in, in oncology, for example, you know, a single biomarker could be an indicator of, you know, 10 tumor types. But here, though, is there any, you know, sort of literature, any evidence for CD40 being a main player, sort of immune dysregulation in other more rare, you know, immune conditions? I mean, there's a whole host of other conditions that CD40 has potentially been implicated in. I think half of those are listed on our website and our, our deck. And we're certainly looking at many of those. I mean, the nice part about being where we are in terms of the revenue, the cash position we have, is that we are, as I said, cash flow positive. And we do have the ability to not only fund Sjögren's through phase III but also continue all the other activities, including BD and potentially looking at other indications, including in CD40. So we're looking at them very carefully. There's a whole host of them. I think at this point, we're not going to. It's quite a competitive area, so we're not going to show the hand, as it were. Rest assured, we're looking very, very carefully about how we could apply and create more value. Well, is there a scenario where you could run, for example, like a basket study, if you will, of a number of different immune conditions that, you know, you'll get the best probability? Or do you have to have sort of an intended approach, like a single indication, and go forward in phase III? I mean, that's a strategy we've used before, actually. And it's quite interesting. I mean, we did it with vixarelimab, the OSM, like I said, an M molecule. And that generated some very interesting data. And certainly, I'm sure, helped to get the value we got when we partnered that with Roche and Genentech. So that was a very compelling area. So that's one option. The other option is obviously just doing another phase II potentially in an area we believe has a high rate of success, especially with potentially a sub-Q dosing modality and the type of, frequency of dosing that John mentioned. So we're looking at both those areas, but that's certainly something that we've done before to quite some success. Yeah. Yeah. And Sanj, you know, you mentioned that, you know, cash flow positive and you guys have been profitable for, you know, past few quarters. Help us with kind of how you balance, you know, the maybe the bottom line and the cash flow with how you could grow, you know, for CD40. I'm just trying to get a sense for, you know, is there still a priority to retain the bottom line, you know, kind of performance? Well, we think about the whole very carefully and very thoughtfully. But I think the focus would be more upon growth and value creation. So while, yes, we are cash flow positive on an annual basis, and obviously, we look at the bottom line very carefully, ultimately, our, our bias is going to be on creating the most value. Yep. In the medium- and long-term and also in the short term. So for us, I think that'll take precedence. You know, we've often said that even when it comes to business development, we've got an incredibly high bar. But we will look at an asset externally that potentially, if it has more value than something you have internally, we'll be open to that. We are incredibly pragmatic. We don't get over emotionally tied to a single molecule. At the same time, having the cash position, it means that we don't have to do a deal that we shouldn't do. So many people do deals just for the sake of doing deals, or they aren't that good. And we're not doing that. So we'll consider all that. So I think that's how we think about it. It's really based on value as opposed to maintaining a certain position or bottom line. Gotcha. And just with respect to the in-house sort of, you know, capabilities, maybe just highlight, you know, is there any particular, you know, platform or differentiation that you guys see from, you know, from internal candidates or that? I mean, we've got a bloody great team. A good, good team can pretty much do anything. You know, I mean, we've, you know, had a phenomenal launch with ARCALYST. Yep. We've executed along our clinical development plans and enrolled on time, if not before time. I think as far as treatment modalities, I mean, we're open. You know, this is a team that's had success now in launching these rare diseases. We've done it with specialty. We've had a long track record in clinical development. We're open to the therapeutic areas. Clearly, we'd like to leverage the large commercial infrastructure we have already now, which is around 85 reps. You know, Sjögren's, there is some synergies potentially. Obviously, the majority of our prescribing base is cardiologists, but about a third is actually rheumatologists, would have a nice overlap with Sjögren's. But beyond that, as far as business development concerned, we're looking at neurology. We're looking at, obviously, cardiology, orphan drug diseases, anything where we believe there's strong scientific rationale, you know, and a real commercial potential where we can drive value. You can't look at one half without looking at the other. Yeah. Yeah. And even among the larger caps, right, you see big companies like Amgen going after more orphan-ish indications that are one click beyond, like, say, RA or psoriasis, right? They're looking at orphan inflammatory conditions. Yeah. Would you say that's a core skill, though, for you guys, cardiology and immunology? But I mean, the hurdle, it must be a little higher if you expand in BD, to go into another therapeutic area. I mean, again, I think a good team can adapt really quickly. Yeah, certainly, there's a lot of muscle memory around IL-1, cardiology, and rheumatology. We've done a lot of neurology in our past. We've obviously done genetic disease and inborn errors of metabolism. We can do those. But I think it's also a team that can expand and move into areas that we're not so familiar with. Yeah. You know, I wouldn't put oncology as one of those top things, but certainly other areas, whether it be, you know, we've done, obviously, dermatology in the past with vixarelimab. Certainly looking at cardiology, neurology, and immunology assets. Okay. Makes sense. All right, guys. Thank you very much. Thank you. You're very welcome.