Kiniksa Pharmaceuticals International, plc ($KNSA)

Okay. We'll continue with the next session. I'm Paul Choi, and I cover the SMID-cap biotech sector here at the firm. It's our pleasure to have Kiniksa here on stage with us for this session. To my immediate left is Ross Moat, Head of Commercial; and then to my far left, John Paolini, Chief Medical Officer. Maybe what we'll do is what we've done in earlier sessions, and I'll let either Ross or John kick it off maybe with some high-level comments sort of on what are the company's strategic priorities for the remainder of the year and going into 2027, and then we can go into Q&A.

Great. Well, thank you very much, Paul. Really appreciate it, and thank you for the invite to be here today and to all of the Goldman team for hosting us at this event. It's a pleasure to be here. And thanks to everyone in the audience and those listening online. Before we go further, I would just mention that today, both John and I will be making forward-looking statements, which are subject to risks and uncertainties, a copy of which can be found in our SEC filings and on our website. So a pleasure to be here. I'm Ross Moat, Chief Operating Officer at Kiniksa Pharmaceuticals. I'm joined by John Paolini, our Chief Medical Officer, and we're happy to go through the Q&A. Maybe to start off with, for those that are not as familiar with Kiniksa Pharmaceuticals, we are around 10 years from the inception, about 5 years out from our commercialization. So we are a commercial stage biotech organization based in Boston. We have ARCALYST in recurrent pericarditis, which was approved from the FDA 5 years ago with a very broad label in recurrent pericarditis. That commercialization has been going incredibly well over the last 5 years since launch up until the Q1 as we most recently reported, which was very strong growth in Q1 of this year, which we can go into in more detail throughout the the Q&A. We actually increased our revenue guidance for full year 2026 from between $900 million to $920 million in net revenue for the year, up to between $930 million and $945 million. We have also been building a robust pipeline, particularly around KPL-387, which you may know is in Phase II/III clinical studies right now. We have several catalysts coming up throughout the rest of the year, including for the Phase II dose finding portion of the study, we're expecting results in the second half of this year. And we've also said that we anticipate moving into the Phase III clinical study by the end of this year also. Additionally, another asset in our pipeline, which is KPL-1161, which is a longer-acting Fc-modified drug which inhibits interleukin-1 alpha and beta, which is also the mechanism for KPL-387 as well that we anticipate moving into the clinic in a Phase I study by the end of this year. Additionally, we're an organization with very robust financials. We're a profitable company, and we have cash reserves of around $468 million as of the end of Q1. So maybe with that, I'll pause and go through the Q&A that you have for us, Paul.

Sure. Thanks, Ross. When I talk with investors, I call ARCALYST was the blockbuster hiding in plain sight that no one seems to sort of recognize, but it's grown and your guidance is approaching blockbuster status for this calendar year. You should comfortably exceed the $1 billion mark next year at the rate you guys are growing. But what I'm curious is that given your label, can you maybe talk about how the evolution in patient behavior has been since ARCALYST has been introduced for RP? And what are you seeing in terms of the mix of new versus repeat prescribers at this stage of the launch 5 years post approval?

Yes, absolutely. So yes, certainly, on one hand, we're very pleased with the commercial progress we've made over the last 5 years. Clearly, we're growing this into a meaningful asset and helping many patients suffering from a very debilitating disease, recurrent pericarditis. But we're actually even more excited by the opportunity that we have ahead. So as you said, we really have line of sight to blockbuster status for this drug. We announced that as of the end of last year, we were around 18% penetrated into the portion of the market, which is those patients that have 2 or more recurrences. So if you imagine that the totality of the target addressable population is about 40,000 patients that suffer in any given year from recurrent pericarditis. That can be broken down into the number of recurrences people suffer. ARCALYST has a very broad label, which covers all 40,000 patients. But if you look at those that have 2 or more recurrences, those that suffer the highest burden of the disease, we -- at the end of last year, we were around 18% penetrated into that patient population, meaning that, obviously, that's driven pretty substantial growth on the commercial side. But the opportunity that is there [indiscernible] more patients in the future is obviously very significant. And that's without even recurrence, which equally are really suffering from the disease or within label of ARCALYST. And in fact, over time, and as physicians have become more and more comfortable and more familiar with prescribing biologics and understanding of interleukin-1 alpha and beta being key cytokines that really drive this disease and the need to control the disease by blocking or trapping those 2 key cytokines has really transformed over time. And we've had more and more use in that first recurrence group. So clearly, that's a big upside population, which is an additional 26,000 out in the 40,000 patient population. So we're pleased with how that has been growing over time. But clearly, we've got a lot of work to do to really fully address the patient population and the opportunity. Certainly, both patient and physician behavior, I think, has changed a lot over the last 5 years, one in terms of the understanding of the disease and what really drives the disease, as I talked mechanistically about interleukin-1 alpha beta. But I think also in how people see the disease from a longevity perspective that this is actually a chronic multiyear disease in the vast majority of patients. And I think historically, before ARCALYST was approved, physicians really used to identify and treat this disease episodically and would treat the flare of the disease. But now I think the understanding has really shifted and the literature has shifted that in recurrent pericarditis, this has really become quite a long disease with the median in the natural history of the disease is 3 years. And 1/3 of the patients -- if patients have 2 or more recurrences. 1/3 of the patients are still suffering from the disease at 8 years -- sorry, at 5 years and 1/4 still suffering from the disease at 8 years when that particular data set finishes. So we know this is generally a multiyear disease and the physicians that have to treat this disease nature through to just treating throughout the natural history of the disease, which is really how ARCALYST was designed to be used. So we think some of those kind of fundamental shifts in how people view the disease, diagnose the disease and treat the disease has really transformed over the last few years.

It really seems like it's evolved, as you said, from acute treatment to more of a maintenance/prevention type model here in terms of the treatment paradigm. With your last quarter's earnings, you also identified a -- called out a pickup in new prescribers. I guess this many years, I guess, into the launch, can you maybe tell us who are these new prescribers? Where they sort of rank, I guess, in your hierarchy or tiering of prescribers? And what is sort of bringing them into the fold? Is it experience with a colleague? Are they in just sort of areas you haven't targeted before? Any color there would be great.

Yes, it's a great question. Really, what we've seen is new prescribers coming in really across the board, across all the different deciles, if you like, or kind of ways of targeting through a variety of institutions, whether it's office-based, community-based academic centers, One thing about this disease is that the patients are pretty widely dispersed across the U.S. And right now, there's a lack of real key centers of excellence for treating this disease. There has been some growth of that over time, but still, generally speaking, is really looked after by a large degree of cardiologists and rheumatologists around the country. So the need to switch on more and more and the ability to be able to switch on more and more doctors is very much there to this new way of treating the disease. So yes, in the Q1 earnings call, we said a couple of things. One, yes, we're 5 years out from the launch. But in Q1, we saw the highest number of new prescribers in any quarter since the time of our launch and the highest number of enrollments, meaning new patients with a new prescription of ARCALYST. So I think that's quite something 5 years out from launch, but I think it really speaks to the opportunity that's there and kind of where we are on the trajectory and the potential that we have ahead for helping more patients. Maybe to give you another metric to think about is that when you look at the total number of prescribers of ARCALYST in recurrent pericarditis, at the end of Q1, we had just more than 4,550 total prescribers, but that's out of a prescriber base of around 25,000 physicians who see a recurrent pericarditis patient in [indiscernible]. So again, clearly, good growth, wonderful that we had the highest number of new prescribers and new patients ever in Q1 of this year and a huge amount of work to do, which is why we're so excited about how many patients we can help in the future.

I am sort of curious, I guess, this is something that hasn't looked at it in a while, but just as you look at your mix of prescribers, how many are sort of cardiologists versus maybe rheumatologists? And are you also starting to see utilization in primary care? I'm just sort of curious of what that might look like.

Yes. So not so much in primary care, but certainly in the specialty setting, the majority is cardiology and to a lesser extent, rheumatology. And I think that's changed a little bit over time where historically, it was rheumatologists that had the bulk of experience of prescribing biologics and cardiologists would often refer to a rheumatology to either rule out underlying etiology of autoimmune conditions and so on or to investigate that further before prescribing a biologic or just through maybe a lack of familiarity and experience for prescribing biologic for the disease. But what we see now is while the rheumatologists are still important and do still prescribe a decent amount of ARCALYST and see these patients for various reasons, the vast bulk really is cardiologists. And I think we've seen a substantial growth in the willingness and the ability for cardiology to really manage this disease with our fair [indiscernible] and look after these patients.

As you look forward, how do you think about what will be sort of the core growth driver in the prescriber base? Will it be these existing prescribers who become repeat prescribers? Or is it going to be finding more and more new prescribers here? And just how do you sort of see that, I guess, ultimately at steady state as you look forward?

Yes. It's a super question. And I think the positive nature of this is that I think really the answer is both and the potential is there for both. As I said, we have around 4,550 total out of a base of 25,000. And then if you take the -- so clearly, we can grow the breadth of prescribing substantially in the future if we continue to execute in the way that we have over the time since launch. So clearly, there's an opportunity there. And then when you look at repeat prescribers, out of the 4,550, we've got around 29% of those physicians now who have prescribed for 2 or more patients. And clearly, that's been growing in both in size and percentage numbers over time. But again, 29%, I think, tells you that there's substantial room for growth. Because this is a rare and flaring disease, we do acknowledge that it takes some time for a physician to see these patients, particularly with how dispersed they are across the U.S. So we see that there's sometimes that lag in how they move from being an initial prescriber through to a repeat prescriber. But it's very, very important to us, one thing that we've been very careful and mindful of since the time of our launch is to make sure that physicians have a very good prescribing experience, meaning that, one, they know how to diagnose the patients accurately and really understand this as a recurrent pericarditis patient rather than just another pericarditis flare or the first index episode. And once the diagnosis is there and they make the decision to prescribe ARCALYST on, they know how to prescribe it. And biologic prescribe it is still relatively new for many cardiologists, maybe outside of the PCSK9. And then very importantly, that they see the patients get on to therapy and they see the type of effects that ARCALYST has. So that means that they see the very strong payer approval rates that we have for ARCALYST. They see the patients get on to therapy and do incredibly well on therapy, which in the main, anecdotally, we hear the type of feedback of the results that we saw in the clinical trials of RHAPSODY, which are really very compelling with a highly efficacious and well-tolerated for ARCALYST. And generally, we hear very good feedback, kind of directly through patients and vicariously through the health care professionals of how well patients feel when they're on therapy. And the importance is really to the 2 sides of the ARCALYST label, which one is how quickly the drug can work to reduce the symptomology of a flare that a patient is suffering and most patients are in a flare when they are prescribed ARCALYST, although not all patients. But then very importantly, the preventative nature over the duration of the disease and patients suffering from this disease really live in fear of another episode happening. So it really impacts their life in a meaningful way, not wanting to travel, not being able to do daily activities. So the need to kind of provide them with the assurance that when they're on drug that they will prevent future recurrences happening is incredibly neat. So if all of those things work incredibly well and then a physician gets a great experience of having prescribed ARCALYST and they hear good feedback from the patients, we believe that encourages them to look and become repeat prescribers and look for the next patients, but as well as the importance of peer-to-peer education. And really, what we've been doing over the last 5 years is creating a new wave of how you treat this disease. And we've really completely changed the treatment paradigm. And we've got a lot more work to do on that. But I think all of the metrics that we share show that we're making pretty strong progress up until the end of Q1 at least.

Kiniksa has been in the fortunate position of not having any near-term immediate recent competition in the RP space. But as you sort of look out there, there are some companies working on assets in development. I think the #1 question that comes up in that category is Ventyx and the recent acquisition there. So maybe, Ross, just from a competitive perspective, who are you monitoring? And for John, as you look at sort of these different mechanisms and different approaches like MLRP, et cetera, sort of what are the pros and cons of these clinical stage approaches?

Yes. So maybe I'll start by just saying we clearly monitor everything. We really kind of established and have been building this marketplace to help patients suffering from recurrent pericarditis. We have other ongoing clinical trials within this disease, which are also of the interleukin-1 alpha beta inhibition mechanism as well. We think that is incredibly important. And we acknowledge that ARCALYST has a very, very high efficacy and tolerability profile of dealing with this disease. That said, clearly, we monitor and we look at competition very carefully. And maybe, John, you might want to make some comments kind of mechanistically on how we think about that.

Absolutely. Thanks, Ross. And yes, Paul, thanks for the question. Yes. So obviously, any innovation in the space is always good, but it needs -- we always think about these things grounded in the fundamental biology. And if you think about the mechanism of recurrent pericarditis, it's driven by the self-perpetuating cycle of autoinflammation that begins with the release of IL-1 alpha localized in the tissue and then the recruitment of the systemic inflammatory response with the role of IL-1 beta. And so what our data have shown and where the science sits is that there's the need to be able to control both interleukin-1 alpha and interleukin-1 beta fully in order to control the disease to its fullest extent over the long duration of the disease. And so some of these strategies that, for example, focus on inflammasome inhibition and the inflammasome is one of the drivers or mediator drivers of IL-1 beta production, that's very far downstream. And it's really for that reason that for our work, as Ross mentioned, we've really doubled down on the concept when we're thinking about how to extend our leadership in the space, is to focus on that dual blockade of interleukin-1 alpha and IL-1 beta, and that's really the inception of the KPL-387 program.

Great. John, maybe you can remind us of what is the Phase II design for your KPL-387 study? How are the doses selected? And how many doses are you testing? And then remind us on sort of what are potential time lines for your dose-finding study to read out here?

Sure. Happy to do that. So as we've talked to -- as Ross mentioned, we're in a Phase II/III study. So the dose focusing portion is the portion that's ongoing now. It's a 4-arm study, and it's designed to really establish the PK/PD relationship of KPL-387 in the disease space. And so it's designed to deliver us development stage appropriate data that inform the PK/PD relationship, but specifically looking at the cadence and magnitude of the initial response as well as the durability of the effect. And that's actually very similar to the work that we did with rilonacept back in Phase II back in 2018. So that trial is ongoing, as you know. And what we've previously guided to is that we expect data in the second half of this year.

Great. Maybe you could just remind us of the dosing cohorts and intervals that you're testing versus the weekly version available with rilonacept here.

Yes, happy to do that, right? So the pharmacokinetics of -- about the long-term nature of this disease. And so the target -- and so a dose-focusing study in that regard is really designed to hone in on the dose and interval that works best. So when you look at our Phase I data, the 300-milligram subcutaneous dose provided coverage above the C efficacious threshold for over 56 days, which is well suited for a 28-day dosing interval with buffer. And so when we designed the dose focusing study, we anchored it on that 300-milligram subcutaneous dose level and then looked -- and the hypothesis then, if you will, is to say, well, making sure that more drug, meaning 300 milligrams biweekly does it deliver more. And then to look at the dose levels that are below, you're looking at the 100-milligram biweekly and the 100 milligram monthly and to see where there is weakness in the coverage. And by doing so, that allows us to affirm to the regulatory authorities that we've identified the dose level that supports the ultimate registration.

Can you maybe remind us of some of the -- it might be a little bit subtle, but some of the differences into how KPL-37 works versus rilonacept. Investors often focus on receptor targeting versus interleukin targeting and just sort of what that might mean in terms of a clinical implication.

Sure. This is a canonical question in any receptor ligand kind of situation, targeting the receptor versus targeting the ligand. As you know, ARCALYST is a decoy receptor cytokine trap. And so it binds interleukin-1 alpha and beta in solution and prevents them from engaging the receptor, whereas -- as we were thinking about how to move forward into the once-monthly target profile and most importantly, in a liquid formulation that would enable self-injection, self-administration in an auto-injector, that really opened up the door to monoclonal antibody technology and targeting the receptor. And so KPL-387 is a monoclonal antibody that targets IL-1R1 or the first chain of the IL-1 receptor. And so therefore, it prevents the binding of IL-1 alpha and IL-1 beta and prevents the assembly of the receptor into a signal competent entity. So importantly, that's kind of how it works. But from an overall perspective, if you actually really think about it, the original work that was done, the seminal work was actually done with an IL-1 receptor antagonist, anakinra, which binds the receptor and does those things. So what was novel actually at the time was that we proved that a cytokine trap would also provide that same effect. And so in the sense, the story has come full circle now, but using a more durable and robust way of targeting the receptor and blocking it over that course of the monthly dosing interval, that really represents the new innovation that we hope to bring forward to patients.

Earlier, you referenced that you have evolved the study into a seamless Phase II/III study. You're currently working on the dose focus -- dose finding sort of portion of the Phase II. But can you maybe walk us through what in your regulatory interactions gave FDA comfort to change this to sort of a seamless trial design? And is it based on established biology here in the IL-1 landscape, your own success in development with RHAPSODY? What just sort of allowed this transition versus sort of a separate stand-alone pivotal study?

Sure. And so one point of clarification. From its inception, this trial was always a Phase II/III clinical trial. So from the point that we brought the protocol forward, even conceived of it for operational efficiency and to move the program forward as quickly as possible. It was designed from the beginning to be a trial that included the dose focusing portion as well as the Phase III pivotal portion and it was all put together into one integrated protocol that was filed at the beginning of the program back some time ago. And so in that sense, this program is rolling out in sequence. And so the Phase II dose focusing portion is the part that we have discussed. But an important element of the design is that the Phase III portion of the study can actually -- we can initiate that independently of the ongoing activity of the Phase II trial. And so as Ross mentioned, we've previously disclosed that we aim to begin the Phase III portion of this trial by the end of this year. And in terms of those regulatory interactions, course that was all filed in one complete package. And so our intent and our belief from those interactions is that the Phase III portion of the trial can, in fact, be pivotal in nature as a single trial and can support the registration of KPL-387 in...

Can you maybe highlight for investors how your Phase III program for 387 differs in what regards versus your prior RHAPSODY study? The landscape has changed, right, since rilonacept has been on the market for several years now. But either in terms of baseline characteristics, any sort of trial specifics, whether it relates to the tapering or anything like that, what would you call out for investors or underscore here?

Yes. that's a great question. So first, just a brief word about the design. And then yes, I appreciate your question because this is really an opportunity for us to continue to innovate and advance the practice of medicine. I want to walk you through a little bit of our thinking there. So in terms of the basic design, what we've already disclosed in our previous packages is that the Phase III portion of the trial is a double-blind, randomized withdrawal placebo-controlled trial, which in a sense, draws on that long experience that we've had in this disease area almost a decade as well as from the RHAPSODY experience. And so in that sense, it goes through the similar segments of the trial where flaring patients are brought into the trial on a range of background therapies. They go through a run-in period where KPL-387 is added on and those oral medications are weaned off. And then the clinical responders are then randomized to either continued KPL-387 or placebo. And then that's an event-driven trial with a primary efficacy endpoint, which really focuses on reduction in risk of recurrence, but it's measured using a time to flare analysis. And so in that sense, that's the package that also then includes other elements. But in terms of the thinking about this, it's actually really important to reflect upon the fact that, again, going back almost a decade when RHAPSODY was designed, the current thinking at the time, which is really based on the 2015 European Society of Cardiology guidelines, which really put corticosteroids in second line after NSAIDs and colchicine. And the science of IL-1 pathway inhibition or the IL-1 pathway really wasn't totally well understood at the time. And so IL-1 pathway inhibition was relegated to essentially third line. And so when we were thinking about how to advance the practice of medicine at the time, we really wanted to kind of work through that transition and break the mold. And so in fact, in its inherent design, RHAPSODY not only -- it was really focusing on that steroid-sparing paradigm. So not only taking patients who are on corticosteroids and trying to get them off, but also even thinking -- and that's the third-line paradigm, but also thinking second line, how do you take patients that are on NSAIDs and colchicine and actually obviate the need for them to even go on corticosteroids altogether. And so that's what RHAPSODY proved is that, that could be done and that, that could be done as a monotherapy. So that's what then became the trigger point in April of 2021 with the availability of rilonacept that changed the practice of medicine towards -- moving forward towards second-line use of IL-1 pathway inhibition, specifically rilonacept. And the RENS registry has chronicled that advancement over time. And then ultimately, that was affirmed by the 2025 American College of Cardiology concise clinical guidance, which positions IL-1 pathway inhibition in that regard. So that's kind of where we are right now, which is actually ideally positioned then with the KPL-387 program to continue to innovate. So it reflects and recognizes that existing population, but then it allows us because of our global reach, where there's a range of different clinical practices across the different geographies and planting -- and putting the trial in all of those different geographies allows us to collect data and inform the practice of using now what is potentially a once-monthly IL-1 pathway inhibitor now in both flaring patients in both second [indiscernible] across a range of different currently available therapies for treating [indiscernible] since the KPL-387 program is positioned to really move the clinical practice of recurrent pericarditis forward into the 2030s, and we're very excited about that.

I want to ask a little bit more on patient baselines. Ross earlier spoke about how ARCALYST is being increasingly used in first recurrence patients but when you guys ran the RAPSODY study, I think you can correctly assume most of these patients were second or third recurrence type patients. So with more sort of first recurrence patients coming into the fold here, does that potentially change or to some degree, the outcome of your Phase III study if more first recurrence patients are enrolled in your Phase III portion?

Yes. So it's important to recognize the fact that when RHAPSODY was designed and run, the use -- the thought process around second -- patients with 2 or more recurrences was not necessarily because of any particular practice element. But it was really about the design of the randomized withdrawal portion of the trial and to make sure that patients came in meeting certain criteria with regard to the NRS score and the CRP elevation and to make sure that when they withdrew from drug that they would be able to briskly reach that same spike and go on to bail out therapy. And those are the fundamental principles of a randomized withdrawal clinical trial. It's also important to note that while that was the way that the trial was conducted when the time came for the labeling of rilonacept, rilonacept was granted -- or ARCALYST was granted a broad label. So it didn't necessarily -- it didn't require having 2 or more recurrences. It just required the disease recurrent pericarditis. And so the use of ARCALYST in patients who are at their first recurrence and coming right off of their incident episode, that is totally on label. So it doesn't necessarily require a clinical trial to study that. What we have done is we've studied that, for example, in the [indiscernible] registry and demonstrated that the benefit of first-line use versus second or third line use, it's all the same because the goal is to maintain disease control. And so in that sense, it's not necessary to include randomized withdrawal clinical trial, but we do have other ways that we study these things and clinicaltrials.gov is always -- as we talk about the specifics of the design of the novel trial, it's a great place to look for the elements of the inclusion/exclusion criteria and endpoints both now as well as going forward.

Great. We're coming up on time here. So I want to touch briefly on 1161. You guys have said not much on it, but maybe can you address how maybe at a high level, it differs from 387 or ARCALYST, sort of what could it do in terms of addressing unmet need in this patient population for convenience, a better dosing interval, more on the company side in terms of scalability and manufacturing? Just maybe what are some of the high-level characteristics here...

Maybe I'll deal with at least the mechanistic attributes of that. So 1161 is a program we're very excited about. There's a great opportunity to do better for patients. And it is also an IL-1 receptor antagonist. So it targets IL-1R1. It has -- and it's also, therefore, designed to be in a liquid formulation. The additional attribute is that it has Fc modifications that increase the circulating half-life. And so the target product profile then becomes ostensibly once quarterly dosing rather than the once-monthly dosing, again, with self-administration in the auto-injector. And so that really opens the door to a range of auto-inflammatory diseases, as you know, that are mediated by interleukin-1. And so this is a highly competitive space, though. And we've talked about the fact, and Ross actually mentioned that we're starting Phase I expect to start that at the end of this year. And so given the competitiveness of the space, we have -- we are yet to disclose what exact indications we're thinking about for 1161, but we do want to highlight the enormous potential that this has for patients.

Great. Maybe sort of last question here in the minute we have left, Ross, as you sort of think about the catalyst path and the story for Kiniksa that you want to promote with -- address to investors in the next year, what would you highlight?

Yes. Well, thank you, Paul. It's great to be here and to be on the stage with you and addressing the audience. So thank you again for inviting us here today. Kiniksa is an organization, one that never rests on our laurels. We have huge potential ahead, and we are very excited about the future, both commercially and what we can do across our pipeline. We've spent the last few years really laying very solid foundations for the business. You say now we are a profitable organization. We have strong cash reserves, a good financial profile, a growing commercial assets and a healthy portfolio of drugs that we're progressing as rapidly as possible through the clinic. So we're incredibly excited about the future. We remain very focused on value creation and having the optionality across our business to go in different directions to really focus on where we believe we can create value for all of our stakeholders and including patients. So we're pretty pleased with where we are right now, but we're even more excited about the future.

Great. We'll end it on that note. My thanks to Ross and John for joining us today. Thank you.

Thank you. Appreciate it.