Kiniksa Pharmaceuticals International, plc (KNSA) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Rilonacept Analyst Day conference call. [Operator Instructions] Please be advised that today's conference may be recorded. [Operator Instructions] I would now like to hand the conference to your speaker today, Mr. Mark Ragosa, Head of Investor Relations. Thank you. Please go ahead.

Good morning, and thank you for joining Kiniksa's webcast covering the burden and unmet need of recurrent pericarditis as well as the potential for rilonacept to treat patients suffering from the disease and our strategy to bring this treatment to patients. The information we present today can be found through the investors and media section of our website. Turning to the agenda. Our CEO, Sanj Patel, will start with an introduction. We'll also hear a first-hand account of the patient journey and learn more about the burden of recurrent pericarditis, the current treatment paradigm and the unmet need from Dr. Paul Cremer of the Cleveland clinic. John Paolini, Kiniksa's Chief Medical Officer, will review the highly statistically significant data from RHAPSODY, our pivotal Phase III trial in recurrent pericarditis. And Matt Magestro, Head of Value and Access, and Qasim Q Rizvi, Chief Commercial Officer, who will detail prevalence as well as the addressable opportunity and our launch strategy. Finally, Sanj will return for closing remarks before we start the Q&A session. Before getting started, please note that we will be making forward-looking statements today that are subject to risks and uncertainties that may cause actual results to differ materially from these statements. A review of these statements and risk factors are found on this slide as well as under the heading of Risk Factors in our SEC filings. With that, I will turn it over to Sanj.

Thanks, Mark. Good morning, everyone, and thanks for dialing in. It's an exciting day today. We are jolly happy to be discussing rilonacept and recurrent pericarditis with you today. The potential of rilonacept coming the first FDA-approved treatment for recurrent pericarditis will be an important step forward for patients suffering from this debilitating and painful autoinflammatory cardiovascular disease. Five years ago, we set out to build a company focused on modulating the immune system to help patients suffering from devastating and debilitating diseases. As well as having a crack team, we've assembled a sequential pipeline of well-designed drug candidates. All of our assets are based on strong biologic rationale, or validated mechanisms, and they target underserved conditions are not for the potential for differentiation. To date, we have carefully and thoughtfully allocated our capital relative to our opportunities. We've executed on our announced time lines and enhance the value of each of our 4 assets, which all have the potential for multiple follow-on indications. In addition to advancing rilonacept in recurrent pericarditis to a pivotal Phase III study, we've made significant progress across our pipeline since founding the company. We received the first U.S. IND for the evaluation of mavrilimumab, or Mavri, in giant cell arteritis. The FDA recently granted Orphan Drug designation for Mavri for GCA. And we expect data from the resulting Phase II study in the fourth quarter of this year. We also received a U.S. IND for the valuation of Mavri in severe COVID-19 pneumonia and hyper inflammation, for which we are currently enrolling a Phase II/Phase III study. In the fourth quarter, we expect to have data from our placebo-controlled investigation. We also advanced Vixarelimab or Vixa and KPL-404, which is our anti-CD40 program into the clinic. Early this year, we announced that our Phase IIa study of Vixa in prurigo nodularis met its primary efficacy endpoint with statistical significance. We plan to initiate a dose-ranging Phase IIb study for Vixa in prurigo nodularis in the fourth quarter of this year. And we're also conducting a Phase I study for KPL-404 and expect Phase I data also in the fourth quarter. Slide 8 gives you an overview of rilonacept. It's a once-weekly IL-1 alpha and IL-1 beta cytokine tract. Which is already an approved biologic in the United States for CAPS, an ultra-rare genetic autoinflammatory disease. Kiniksa licensed rilonacept's from Regeneron in 2017 to focus on diseases thought to be mediated by both IL-1 alpha and IL-1 beta, including recurrent pericarditis. The FDA granted breakthrough therapy designation for rilonacept for recurrent pericarditis in late 2019 and Organ Drug designation to rilonacept for pericarditis in 2020. Our pivotal Phase III study called RHAPSODY met its primary and all major secondary efficacy end points with a high degree of statistical significance. And upon receipt of FDA approval for rilonacept, Kiniksa will assume the sales and distribution of approved indications in the United States, which include CAPS and evenly split profit on sales with Regeneron. So before I hand it over to Dr. Paul Cremer, we'd like to show you a video, highlighting the sheer burden and impact of recurrent pericarditis on the lives of patients. This is Nadine's story. [Presentation]

We thank Nadine for sharing her story. We'll now turn the call over to Dr. Paul Cremer of the Cleveland Clinic, who will walk you through the pathophysiology and burden of recurrent pericarditis in more detail. Paul?

Good morning, and thank you. I'm Paul Cremer. I'm a cardiologist and a cardiovascular imager at the Cleveland Clinic, where I'm also the Associate Program Director for our cardiovascular training program. And I'd like to thank you for sharing that patient story. As someone who cares for a lot of patients with recurrent pericarditis that unfortunately was very typical of the degree of disability and vicious cycles that these patients experience and really highlights my passion to try and identify better therapies for this group of patients. So today, I'm going to be discussing recurrent pericarditis, the need for novel therapies for debilitating autoinflammatory disease. Next slide, please. So related to this talk, my disclosures include that I've been on scientific advisory committees for Sobi and Kiniksa Pharmaceuticals. I have directed core imaging labs for clinical trials involving rilonacept. And of course, the views expressed here on my own and not necessarily those of my employer, the Cleveland clinic. Next slide, please. So my objectives in the next 20 minutes are fairly straightforward. I'll briefly touch upon pericardial anatomy and histology. I'll then transition to talk a little bit about the burden of disease. And next, I'll touch upon what our current treatment paradigm is, and then segue into the pathophysiology of pericarditis and what's emerging as the essential role of interleukin-1 and then conclude by mentioning the need for targeted therapies. So just to begin with some basic anatomy. The pericardial space consists of 2 layers, which form a sack around the heart and normally contains up to 50 milliliters of serous fluid. The pericardium extends superiorly to involve the proximal grade vessels and post sterile around the left atrium. So most of the left atrium is extra pericardial. And pericardial also has ligaments attachments to the sternum and the diagram. Next slide. So as I mentioned, the normal pericardium consists of 2 layers: the parietal and the visceral pericardium, the parietal pericardium, which you can see in panel A, is usually less than 2 millimeters in thickness and is composed of bundles and-- of collagen bundles, which you can see in yellow, interspersed with elastic fibers, which are shown in black with a very amount of fat, which you can see in the right at the bottom part of the slide, extending towards the mediastinum. In Panel B, you can see the visceral pericardium or also called the Epicardium, which consists of -- typically of a single layer of mesothelial cells, atopic basement membrane and also shown and see, there's a variable amount of fat involving the epicardial tissue. Next slide. So what happens when patients develop pericarditis? Well, histologically, there's a fairly expected progression. So first, there's deposition of fibrinous material and recruitment of inflammatory cells. Subsequently, there's disintegration of the mesothelial cells. And then there's organization with neovascularization and in growth of fibroblast and this neovascularization is important to highlight because it's a way for us to image inflammation with cardiac MRI, which I'll touch upon later in the talk. And then finally, there's loose fibers adhesions that develop and heal pericarditis. Next slide. So then to speak a little bit about the burden of disease. So who are the patients that get pericardial disease? Well, acute pericarditis is quite common. The majority of these patients fortunately will have resolution, though some patients will progress to involve the myocardium, maybe 10% to 15% with mild pericarditis or perimyocarditis. But the patients we're really focusing on today, as was highlighted in that patient's story are the patients who have recurrences and multiple recurrences. Next slide. So as I mentioned, acute pericarditis is a common reason to present to the emergency department. So in the U.S., there's 27.7 new cases per 100,000 per year. Of these patients, recurrences develop in 15% to 30%. And a smaller number of patients will go on to develop cardiac tamponade or constriction with wide variations in the reported incidences based on the publish data. Next slide. So what are the risk of recurrence? Well, we know that short-term high dose corticosteroid use leads to recurrence, which is something we too often see patients go to the emergency department, they get a Medrol dose pack and then they are often heading towards a cycle of recurrent pericarditis. The lack of colchicine therapy, which is efficacious, in pericarditis will increase the risk of recurrence. And then patients who have a more severe disease characterized by either incomplete response to insets or a high C-reactive protein. Next slide. So then to speak about what our current treatment paradigms are for pericarditis. So with acute pericarditis, we typically give patients an NSAID, ibuprofen or aspirin for weeks and colchicine in for 3 months. At the first recurrence, our typical approach would be continued NSAIDs for weeks to months and colchicine for a longer duration. And the duration of the NSAIDs often depends upon following the C-reactive protein, which is invariably elevated in these patients, when the C-reactive protein has normalized, we would then typically taper the insets, but certainly want to continue the colchicine for a longer duration of time. For patients that have disease that's either resistant to colchicine, so they're having symptoms despite colchicine and NSAIDs or have had a second recurrence. This is typically where we would add prednisone, given the deleterious effects of long-term use of prednisone, we really need steroid-sparing agents at this phase of the disease. And certainly, in our current paradigm and third recurrences when you would think about a steroid-sparing agent. So what I think an important concept in recurrent pericarditis is to better characterize the phenotype not only to inform our treatment, but our duration of therapy. Next slide, please. So I think there's really 2 questions that come up. One is, does this patient have an inflammatory phenotype? And I would say most of these patients do, and that's characterized by an elevation in the C-reactive protein. And I think an important point to recognize is that inflammatory phenotype is quite common in patients that we typically thought of as idiopathic or viral pericarditis. And also in patients who have another common cause of recurrent pericarditis related to prior cardiac injury. So patients who had prior cardiac surgery, prior percutaneous coronary intervention or prior EP procedures are also at risk for developing recurrent pericarditis and once those patients develop recurrences, their phenotype, their clinical symptoms, their degree of inflammation is really indistinguishable from patients who have idiopathic pericarditis. The second important point is, what do we anticipate as the expected duration of treatment? Well, what we're finding is that these patients often need prolonged durations of treatment. So treatment for greater than a year, and there's emerging evidence that the use of cardiac MRI can help inform how long to treat these patients with immunosuppressive agents. So here, in this picture, you can see cardiac MRI and in white, there's severe hyper enhancement of the pericardium. So now I'm going to transition to talk about the pathophysiology of recurrent pericarditis, and specifically how it relates to in interleukin-1. So I think if we think of immune dysregulation, the rheumatologist are very familiar with this continuum of autoimmune and autoinflammatory disease, be it organ specific or more systemic. And this is a new concept for us in cardiology, I would say, within the past several years in becoming more of our clinical practice as we treat these patients. I think an important point to -- and again, there's a lot of overlap here, but as a general concept, we think of autoinflammation is driven by endogenous danger signals, perpetuated by inflammasome-induced interleukin-1 and interleukin-18 production. Conversely, autoimmunity involves activation of TMB cells characterized by a more predominant type 1 interferon signatures. And the biologic agents that we choose for these diseases will be distinct. And I think what is emerging is the understanding that recurrent pericarditis is a prototypical organ specific autoinflammatory disease. Next slide, please. So it's led us to write a couple of prospective pieces really questioning the diagnosis of idiopathic pericarditis because idiopathic is a term that helps neither the clinicians nor the patients and just engenders a lot of confusion and frustration, again, as was highlighted in the patients then yet. So I think, in particular, as it relates to recurrent pericarditis, and most of these patients based upon what we know now, it's more appropriate to refer to it as autoinflammatory or recurrent autoinflammatory pericarditis. And this really converges on the central role of the inflammasome and recurring pericarditis. So what happens is that there is binding of either pathogen associated molecular patterns or damage associated molecular patterns to receptors at the cell membrane that lead to downstream signal transduction and eventual translocation and beta to the nucleus and transcription of interleukin-1 and further activation of the NLRP3 inflammasome. Now there's a second signal that recruits ASC to activate the NLRP3 inflammasome and NLRP3 inflammasome converts pro-caspase to caspase one, which leads to systemic secretion of interleukin-1 beta. And as was mentioned at the outset, rilonacept has an approved indication for CAPS, which is a disorder involving this inflammasome, which also seems central to recurrent pericarditis. So what about the therapies that are in our current armamentarium for pericarditis? Well colchicine is, in fact, an inhibitor of the inflammasome, so by inhibiting microtubules can inhibit receptors involved in inflammasome activation as well as caspase One. And we know prednisone was a very broad immunosuppressant, but also inhibits NF Kappa beta. So the question is, what do we do for patients where the inflammasome activation is too much, is overwhelming and driving the recurrent pericarditis. And I'll touch upon that in a few minutes, but I first just wanted to provide some historical perspective. And how did we even get to thinking about colchicine in recurrent pericarditis. Well, it's really because of the overlap with these inherited or autoinflammatory conditions such as CAPS and familiar Mediterranean fever. So this is initial report of the use of recurrent pericarditis in the lands in 1987, in a handful of patients. And this was basically tried because of the reported efficacy of colchicine in the recurring poly serositis in familiar Mediterranean fever. Next slide, please. And if you go back even a decade prior to 1977, this was work from Anthony Letai Lab showing the efficacy of colchicine and familiar Mediterranean fever that patients can recognize the prodrome of their attacks and some patients can consistently abort their attacks with short courses of colchicine. Next slide, please. So this really brings us to the role of interleukin-1 alpha and interleukin-1 beta in autoinflammatory cycle of recurrent pericarditis. So as I mentioned, interleukin-1 beta is secreted systemically, but there's also a lot of excretion of interleukin-1 alpha at the site of tissue injury, which can bind to tissue macrophages and endothelial cells. And it's the binding of interleukin-1 alpha and interleukin-1 beta, through increasing white blood cell adhesion, monocyte infiltration and capillary league that can lead to these recurrent cycles of pericarditis and debilitating disease for our patients. Next slide. So how do I think about targeted therapies? So the first question is this an autoinflammatory phenotype? So at any point, has this patient's disease been characterized by elevated CRP and systemic symptoms. And again, most patients who have either -- what we have traditionally called idiopathic pericarditis or post cardiac injury syndrome or post-pericardiotomy pericarditis, have an inflammatory phenotype. And then in those patients, I think we can use interleukin-1 antagonism to avoid prolonged courses of corticosteroids. As I mentioned, by the time that patients get in these cycle to pericarditis, they will need prolonged durations of therapy, certainly for more than a year. And often cardiac MRI for us clinically is helpful to guide the duration of that therapy. And then there's another group of patients, who will consistently have recurrences with tapering of corticosteroids. So on a moderate to high-dose of corticosteroids, they can control the disease, but have all the deleterious side effects of prolonged corticosteroid use for cardiovascular side effects, diabetes issues with osteoporosis and many others. And every time they come down to a certain dose of prednisone, they reliably flare. And so that's a patient -- that's a very common clinical scenario and a patient that also has an inflammatory phenotype, even though the CRP may be suppressed by the concomitant use of corticosteroids. And interleukin-1 antagonism, certainly can facilitate the tapering of corticosteroids in those patients. So I'll conclude by touching upon the results that have been previously presented of the Phase II study of rilonacept for recurrent pericarditis. So this was an open-label Phase II study of 25 patients with recurrent pericarditis, importantly, it involved patients who are either having an active recurrence or corticosteroid dependent without active recurrence and included patients who had idiopathic pericarditis or patients who had post-pericardiotomy syndrome. And these patients received 6 doses in an open-label treatment period. And then -- so over 6 weeks of received rilonacept and then an extension period of an additional 18 weeks. With the primary outcome of looking at decrease in pain and CRP, and disease activity after corticosteroid taper. Next slide, please. So what we found is that rilonacept normalized CRP in an average of 19 days. And in patients who are having an active recurrence quickly got these patients to be quiescent and free of symptoms. Next slide, please. And then if we followed out into the extension period of the 13 patients who were on corticosteroids, 11 were tapered discontinued completely, whereas the other 2 were continuing to taper their steroids during the extension period. So I think this Phase II open-label experience taught us that we can quickly get a patient in remission, who's having occurrence of pericarditis with rilonacept. And it allowed us to develop a comfort level in tapering corticosteroids effectively without any risk of recurrence. So there's no recurrences during follow-up in these patients. If we look at some of the secondary outcomes, the mean quality of life scores improved both physical and mental domains in this Phase II clinical trial. And as our imaging surrogates showed us were consistent with the overall results of the study. And that pericardial effusion improved in 6 out of 7 patients and the pericardial delayed hyper enhancement, which is, again, is the way that we primarily image inflammation with cardiac MRI in patients with pericarditis resolved in 6 of 8 patients. Importantly, if you look at the annualized incidence of pericarditis before the study and after the use of rilonacept, it decreased from 3.9 to 0.18 episodes per year. So a dramatic reduction in the patient population that was very debilitated with recurrent pericarditis. So to conclude, I would say we now understand recurrent pericarditis to be an autoinflammatory disease and that these patients develop debilitating recurrences that interleukin-1 has been shown to play a key role in driving that inflammation. And the downsides of corticosteroids are very well known, nonspecific immunosuppressive action with many, many side effects. So target immunomodulatory approaches, locking in interleukin-1, signaling have certainly shown promise in recurrent pericarditis. And as we've been more to come, I think, along those lines. So I'll stop here. I'm happy to take any questions in the discussion at the end. And I appreciate your time, and I'll turn it over to Dr. John Paolini.

Thank you, Dr. Cremer. I will now review the Phase III RHAPSODY data, which we previously presented publicly on June 29, 2020, which have been posted on the Kiniksa website. RHAPSODY is a global pivotal Phase III study of rilonacept treatment in recurrent pericarditis, which utilizes a randomized withdrawal design, well-known in rare diseases. The co-principal investigators were Dr. Allan Klein of the Cleveland Clinic and Professor Massimo Imazio from the University of Torino in Italy. Acutely symptomatic patients who are failing their background regimen of NSAIDs culture or steroids were enrolled in a 12-week single blind run in period during which they received weekly rilonacept, while background pericarditis medications were tapered and discontinued. In the pivotal portion of the study, clinical responders on monotherapy rilonacept were randomized one to one to either continued weekly rilonacept or to placebo in a double-blind, randomized withdrawal period. The primary efficacy endpoint was time to first adjudicated pericarditis recurrence during the randomized withdrawal period, the duration of which was events driven. Patients who experienced an eligible recurrent pericarditis event during the randomized withdrawal period could be given bail out open-label rilonacept and remain in the study until the end of the randomized withdrawal period. Following the receipt of breakthrough therapy designation and based on a type B interaction with the FDA, we expedited the time line to data by triggering the close of the randomized withdrawal period after the minimum 22 adjudicated events had accrued. Patients completing the randomized withdrawal portion of the trial were given the option to continue open-label rilonacept in the 24-month long-term extension period, allowing these patients with recurrent disease to remain on treatment as well as helping us accrue on drug exposure and informing optimum treatment duration. RHAPSODY was a well-balanced study and the baseline demographics of the patients upon presentation shown on the left are representative of the real-world pericarditis population. In terms of prior recurrent pericarditis history, patients qualify for the trial with a mean of approximately 5 pericarditis episodes with a mean duration of disease of 2.4 years and experiencing a mean of 4.4 episodes per year. Underlying original ideology was predominantly idiopathic, which means usually post viral, and there was proportional representation of post-pericardiotomy syndrome meaning those who had prior cardiac surgery or percutaneous intervention. The proportions of patients receiving NSAIDs, colchicine and corticosteroids at the time of enrollment are shown here. Of note, these patients were experiencing an acute recurrence despite their standard of care treatment. 80% were on colchicine and almost half were on corticosteroids with 1/3 to 1/2 of those patients being on steroids longer term. Looking at the magnitude of disease on presentation, patients were experiencing pericarditis pain on the NRS scale of just over 6 out of 10. See reactive protein, the marker of inflammation severity was over 6 milligrams per deciliter with normal being 0.5 milligrams per deciliter and the minimum threshold for entry being 1 milligram per deciliter. Other objective manifestations of pericarditis listed here were represented as expected. Finally, the randomization of the study was well balanced between the rilonacept and the placebo arms. Here, you have a consort diagram detailing subject to the disposition in RHAPSODY, 86 patients enrolled in the running period and 92% completed the run-in period. There were rapid and sustained reductions in both reported pain and inflammation as early as after the first dose. Median time to pain at a score of 2 or less was 5 days. And median time to CRP normalization was 7 days. Median time to treatment response, which combines pain and CRP response was 5 days. Turning to tapering and discontinuation of standard of care treatments, time 2 monotherapy rilonacept was 7.9 weeks, 2 weeks earlier than the protocol specified maximum of 10 weeks. From a randomization efficiency standpoint, only 4 patients discontinued from the run-in period for adverse events and only 3 patients did not meet the formal NRS for CRP criteria for randomization. 61 patients were randomized, 30 to rilonacept and 31 to placebo. At the time were the randomized withdrawal portion of the trial disclosed early, as I mentioned, there were 15 patients who are still completing the run-in period these patients were transitioned directly to the long-term extension period, as shown on the right. 60 of the 61 randomized patients completed the randomized withdrawal period and 74 of 75 eligible patients continued into the now ongoing long term extension. The study overwhelmingly met its primary efficacy endpoint, time to first adjudicated pericarditis recurrence in the randomized withdrawal period. This Kaplan-Meier curve shows rilonacept patients in blue and placebo patients in red. There were 25 positively adjudicated recurrent pericarditis events in the primary data set. Median time to first recurrence in the placebo arm was 8.6 weeks after randomization, consistent with the expected washout pharmacokinetics of once-weekly rilonacept-sedi state. Median time to first recurrence in the rilonacept arm could not be calculated as there were not enough recurrent events in the observation period to allow for the number to be calculated. The hazard ratio of 0.04, means that patients randomized to rilonacept experienced a 96% reduction in the risk of a recurrent pericarditis event with a highly statistically significant p-value of less than 0.0001 shown here. 2 additional observations about the curves, in the rilonacept arm, there were only 2 recurrent events, and these occurred after brief temporary study drug interruptions of 1 and 3 weekly doses. In the placebo arm, almost half of those who went on to suffer a recurrence events did so within the first month after atomization, underscoring the tenacity of recurrent pericarditis. Finally, of the 25 recurrent events, 24 received bailout rilonacept. And for these patients, there were no reported pericarditis recurrences for the remainder of the study. These data demonstrate that in this study of patients with recurrent pericarditis, remaining on continued pericarditis therapy resulted in continued clinical response and prevention of recurrent events. Major secondary efficacy endpoints in the randomized withdrawal period were also highly statistically significant. These major secondary efficacy endpoints were calculated in those patients who had at least 16 weeks of participation in the randomized portion of the study with week 8 and week 24 data being reported as a sensitivity analysis. On the left-hand side of the slide, using the objective study criteria of maintaining an NRS less than or equal to 2, CRP of less than or equal to 0.5 milligrams per deciliter, while on monotherapy and without a recurrence 81% of rilonacept recipients maintained clinical response at week 16 of the randomized withdrawal period compared to 20% of placebo recipients with a p-value of 0.0002. In the middle panel, this endpoint was taken from a patient quality of life perspective, utilizing a patient-reported, pericarditis symptom survey as we see a consistent result. 81% of rilonacept patients experienced absent or minimal pericarditis symptoms at week 16 of the randomized withdrawal period, compared to 25% of placebo recipients with a p-value of 0.0006. Finally, in the far right panel, also from the patient perspective, we looked at the percent of trial days through week 16 that patients reported no or minimal pericarditis pain. For rilonacept recipients, that was 98% of trial days being pain-free or at most experiencing minimal pain versus 46% of trial days for placebo recipients with a p-value of less than 0.0001. Rilonacept was well tolerated in the study with adverse events consistent with the FDA-approved label for the treatment of cryopyrin-associated periodic syndromes or CAPS, there were no deaths or SUSARs serious adverse events were unrelated to study drug. The most common adverse events were injection site reactions and an increase in infections, predominantly in the upper respiratory tract such as URIs and nasopharyngitis shown in the right panel as expected and consistent with the ARCALYST its label. Given the efficacy outcomes shown in the prior slides, we believe that the benefit risk in this clinical trial favors rilonacept. I will now turn it over to Matt Magestro to review pericarditis epidemiology. Thank you.

Thanks, Dr. Paolini. My name is Matt Magestro, and I head up the Value and Access function here at Kiniksa. Today, I'll provide a brief overview of the work we've done to understand the U.S. recurrent pericarditis population. It begins with an estimate of the number of patients, who experienced a pericarditis episode each year. To do this, we conducted a study using the National center of Health statistics, health surveillance databases that sample and project national inpatient, ER and ambulatory in commerce by diagnosis code. Using a methodology developed by researchers at the centers for disease control, we looked at annual totals for all types of pericarditis over a 10-year period to estimate that there are approximately 160,000 pericarditis patients annually. This study provided supporting evidence for the orphan drug designation that we received earlier this year. The next step is to estimate the portion of the patient population most relevant for a treatment like rilonacept. In Western markets, approximately 75% to 80% of cases are considered idiopathic and that the underlying cause is actually not known, these are typically presumed to be post viral cases. The estimate of approximately 125 patients annually corresponds to the ideologies of patients studied in the RHAPSODY trial and reflects patients with an inflammatory fee. Based on generally accepted recurrence rates at which we confirmed in 2 separate U.S. database studies, we estimated that the size of the recurrent pericarditis population have those that experience a recurrence in any given year are approximately 40,000 patients, of which 14,000 patients are experiencing their second or more recurrence due to persistent underlying disease and inadequate response to conventional therapies like NSAIDs, colchicine and corticosteroids. Of note, the 14,000 patients is a dynamic patient population where approximately 7,000 patients newly experienced their second recurrence each year. While for other patients in this group, the disease resolves often after several years of suffering. The 2 U.S. database studies that I mentioned supporting our estimates of the patient population were presented at the American College of Epidemiology in the American Heart Association conferences, respectively. The poster presentations are available on our website and manuscripts for both studies are in development. At this point, I'd like to transition over to our Chief Commercial Officer, Qasim Rizvi.

Perfect. Thank you so much, Matt. So now turning to the commercial opportunity. Based on our ongoing market research and launch preparation activities, we really continue to get more and more excited with the rilonacept opportunity. And at launch, our focus is going to be on the patient population with the greatest unmet need, and you see those patients on this slide. And these patients are the refractory patients, patients with multiple relapses, as well as patients that are steroid dependent, and there are approximately 14,000 patients who meet these criteria. And in fact, these patients were really well represented in RHAPSODY. Now the key reason to focus on these patients at launch is not only the fact that they have the highest and immediate unmet need, but also because they are easy to identify, and they provide a clear call to action for physicians to prescribe. And it's important, we believe to focus on this patient population to really ensure a well-executed launch. Now with that being said, we do believe the data from RHAPSODY are really compelling and as physicians gain experience over time, they could broaden utilization, especially for patients who have a single recurrence but associated with a high-risk factor, such as the cardiac tamponade in infusion or constriction. However, that will be a decision between the physician and the patient and all our promotional efforts will be within the FDA-approved label. Next slide, please. So now briefly turning to the unmet need. You saw from the data that was presented by John, rilonacept treatment in the pivotal Phase III generated data on what we believe are the 3 -- the 4 most important areas of unmet need, and those are shown here on this slide. So the need for rapid resolution of acute episode, the need to prevent future recurrences, the need for a steroid-sparing regimen and then the need to improve overall quality of life. Now the way we started rilonacept was to provide data not only to inform the treatment and prevention of disease recurrence, but also to potentially shift the treatment paradigm and move upstream to avoid the need for initiating steroids. In this way, we hope to address the unmet need both for the treatment and prevention of recurrent pericarditis with a targeted therapy. Overall, we believe that rilonacept if approved, has the potential to become the standard of care in recurrent pericarditis and set the bar for all of the therapies, especially given the robustness of our Phase III rapidly study, the compelling efficacy data, plus the fact that we have a well-tolerated weekly subcutaneous regimen. Next slide, please. So now turning to our launch strategies. It's a busy slide, but I'll walk you through it. So we are thinking about the rilonacept launch as a focused and targeted effort, where we want to optimize the customer experience. We believe this will be critical both for patient acquisition as well as patient retention. So we have already started working closely with all our key stakeholders to show our commitment to advancing the scientific and medical understanding of recurrent pericarditis to try to achieve better patient outcomes. This includes our RHAPSODY study as well as real-world evidence generation, which will help create the right market environment for launch. Additionally, through a data-driven market assessment, we have developed a highly efficient launch model that's built around 4 key strategic imperatives. The first of which is establishing the unmet need and really ensuring recurrent pericarditis is viewed as a serious and debilitating disease that is primarily driven by IL-1. The second strategic imperative is ensuring rilonacept is viewed as the product of choice for the treatment and prevention of recurrent pericarditis. The third relates to reimbursement. And ensuring broad patient access at a price that reflects rilonacept value as first-in-class IL-1 inhibitor of inflammation. And the final strategic imperative is around robust patient support programs. To optimize the patient and customer experience with the rilonacept as well as Kiniksa. Now given that this is going to be our first launch, we are not only building scalable capabilities to support a targeted launch but also want to establish the infrastructure for future growth and success. Next slide, please. Okay. So let's take a deeper look at our first strategic imperative, which is really to establish the unmet need and ensure recurring pericarditis is viewed as a serious debilitating disease that is primarily driven by IL-1. To support this effort, we did launch the heart of inflammation disease awareness campaign. This campaign helps drive awareness and understanding of current pericarditis as well as the role of IL-1 over production. It also characterizes and communicates the burden of the disease on patients as well as caregivers. And it highlights the need for licensed, safe and effective treatment that resolve the flare and reduce future episodes. Bottom line, we want to build upon and highlight the sense of urgency to do more for patients living with recurrent pericarditis. Now still early days in the launch of this campaign, but even after the first 4 weeks, we have had over 7,000 unique visitors to the website, and we have registered visitors who have opted in to receive more information in the future. Additionally, the site has been visited by over 150 medical organizations from across the U.S., which I think is a great sign of the level of interest and anticipation. Next slide, please. We also know that patients and caregivers will be critical in the success of our launch. So we want the patient community to be educated and empowered to advocate for appropriate care in access to rilonacept. Therefore, we are building a multichannel patient support network, comprised of patient videos, testimonials, social media engagement, patient education efforts as well as access to advocacy. Our goal here really is to accelerate awareness, trial and adoption of rilonacept at the time of approval. And we believe through robust peer-to-peer disease and product education, we can achieve this. In addition, we want the community to view Kiniksa as a trusted partner and a leader in recurrent pericarditis. So for instance, this month, the pericarditis alliance was officially incorporated in New York state. This alliance is fully dedicated to the treatment of pericarditis and the Kiniksa's patient advocacy team has been working closely with the alliance to compliantly support their goals and efforts. Additionally, there are several leading physicians on the Board of the alliance, such as Dr. Allan Klein and Dr. Massimo Imazio. In addition, our patient advocacy team is working to identify potential patient advocates who are willing to partner with us here at Kiniksa to share their experiences and educate others. Really what we're hoping to do here is to amplify the voice of the patient and really put a face on the burden of recurrent pericarditis. Finally, we also -- we also are working very closely with the advocacy groups to set up educational webinars and videos with the goal of having 4 webinars executed between now and Q2 of next year. Next slide, please. So turning to our second strategic competitive, which is to establish rilonacept as a product of choice for the treatment and prevention of recurrent pericarditis. We plan to build a multi prompt collaborative field force. To deliver targeted messages to support rilonacept's adoption. The teams will focus on ensuring there is understanding of the benefit risk profile of rilonacept and also demonstrating the scientific evidence that rilonacept targets the primary mediators of recurrent pericarditis. We will ensure that all our field teams, which will include MSLs sales, patient services and payer teams are aligned and coordinated. We believe that this level of coordination will be critical in bringing value to our customers, and creating the best possible experience for patients and our key stakeholders. Overall, we believe that our Kiniksa One mindset will help us establish credible and compliant relationships with our target customers. Next slide, please. Now one of the things we pride ourselves on here at Kiniksa is in our ability to execute and to help us ensure high-quality execution we have triangulated multiple claims analysis to map out the top treating hospitals and practices. And with a specialty cardiology sales force of approximately 30 reps, we believe we can cover approximately 70% of our target patient population as they are concentrated in about 800 accounts. So at launch we're going to ask our sales reps to initially target the top 10 to 15 accounts in their territory, and this will account for approximately 45% of all recurring pericarditis patients. Now this focus is really important and will help us enable -- reaching the key centers in a timely manner. It also enabled us to provide a high level of support and touch points for the higher volume prescribers. We will then expand to the remaining 30 accounts in each territory. So in total, enabling us to cover 70% of all recurring pericarditis patients. Also, the Kiniksa sales team will have a targeted call plan, and will be responsible for navigating the entire account to identify prescribers and facilitate any required referrals as appropriate. Additionally, the sales force will also be supported by our current MSL team and a highly efficient digital marketing effort. Now on the medical affairs side, our MSLs are already developing strong science-based relationships and leading disease education efforts with cardiologists as well as rheumatologists. And finally, the medical affairs team is planning to launch a recurrent pericarditis registry. The goal of which is to collect real-world evidence and expand our research partnerships with the health care and patient community. And in doing so, we will learn more about the natural history of recurring pericarditis as well as patient outcome. Now given the unpredictability of the COVID-19 environment, we are also working on contingency launch plans to ensure a successful launch really in any environment. So we are monitoring very closely industry best practices and new technologies, how we could potentially leverage to ensure that we have effective and compliant communications with our target customers. So bottom line, we will be prepared to quickly pivot to an increased digital presence and enable compliant remote detailing by ensuring that the CRMs that we build out enable us to do so effectively. Next slide, please. Okay. So now moving on to our third strategic imperative, which is Payer Reimbursement. Here, we are taking a 3 phased approach with payers with the goal of facilitating broad access and affordability. Prelaunch, we are engaging with payers to introduce Kiniksa and highlight our exciting pipeline. We are starting to have detailed conversation around the burden of the disease and the impact that recurrent pericarditis has on the lives of patients. You saw some of that from the video by Nadine. We are also starting to share data and findings from RHAPSODY. The key objective here is to put rilonacept on payer's radar. And to help ensure timely, formulary and coverage determinations with no inappropriate restrictions. So specifically, we are focusing on shortening the time to pay reviews and coverage, ensuring appropriate formulary tiering to reduce patient cost burden and minimizing burdensome coverage restrictions. Next slide, please. Finally, on to our fourth strategic imperative, which is focused on patient services. Now early on in our launch planning, we have determined that optimizing the patient and customer experience with rilonacept as well as Kiniksa was going to be mission-critical. And something that we really wanted to infuse in our thinking and into every aspect of our launch planning. So we mapped out a very detailed patient journey to identify potential challenges as well as opportunities to support rilonacept trial and adoption. The output of the patient journey helps us build our patient support offering, and you see some of those listed on this slide. Ultimately, our objectives are to provide high-touch support for patients and physician's offices, so can minimize any administrative hurdles. And we also want to maximize patient access and affordability through quickly establishing optimal payer coverage and compliantly offsetting patient financial burden. In summary, by focusing on a targeted and highly efficient launch model, which is built around these 4 key strategic imperatives, we believe we will be very well positioned to have a successful launch and help patients living with recurrent pericarditis. Now my final slide here, briefly, just a few comments on price and duration of therapy. So as we start to engage with payers, we will provide them a budget impact model. But just as important is to ensure that payers have a full understanding and appreciation of the burden of this disease and the devastating impact it has on their lives. We believe that the current price of ARCALYST is in line with other specialty biologics as well as products that have breakthrough therapy designation and orphan drug designation. Now in terms of duration of therapy, just a few things to keep in mind, first, the average duration of recurring pericarditis is about 2 years. And there are certain high-risk characteristics that may identify patients who could benefit for longer treatment duration. Now what we saw in RHAPSODY was a median treatment duration of 9 months with a range of up to 15, and this resulted in the 96% reduction in the risk of recurrence. We also saw that patients on rilonacept experienced no or minimal pericarditis pain for 98% of trial days. And additionally, 74 out of the 75 patients continued into the long-term extension, which I think demonstrate a desire to continue longer-term treatment potentially even up to 24 months. Now additional data that supports the potential benefit of longer-term duration, include the fact that the only events that we saw in the rilonacept's arm in RHAPSODY took place in the setting of temporary drug interruption. Also, all patients in the placebo arm who received bail out of rilonacept did not experience a recurrence through the end of the randomized withdrawal period. Additionally, there's a registry data indicating that patients treated for 6 months had worse outcomes compared to patients treated with 9 months. So our initial thinking and assessment is that patients could be treated for 6 to 9 months and some patients may require longer treatment duration potentially 12 months and more. So in closing, I hope this gives you a sense of how we are thinking about the launch, what we believe are the critical success factors to the launch, the strategic imperatives, and why we continue to get more and more excited about the opportunity to help patients living with recurrent pericarditis. So with that, I will hand it back to Sanj for final remarks before we open up for questions. Sanj, over to you.

Thanks, Q, nicely done. As I mentioned earlier, we believe the robust efficacy data from RHAPSODY, combined with the well-tolerated safety profile and the weekly dosing regimen, position rilonacept to be the first FDA-approved therapy for recurrent pericarditis. This would obviously be great news for patients suffering from this debilitating disease and an important milestone for Kiniksa. We believe the 14,000 patients with multiple recurrence annually have the greatest unmet need and represents a clear core to action as we prepare to diligently commercialize this therapy. The market research suggests that the duration of therapy for patients for the first couple of years, as Q mentioned, could be at least 6 to 9 months. And the appropriate treatment duration for some patients, again, as Q has highlighted, maybe 12 months, or even longer. The current gross pricing caps, as Q mentioned, again, is $20,000 a month. This is in line with specialty biologics with great to therapy designation, orphan drug destinations and the high unmet need in recurrent pericarditis. In summary, we're looking forward to the potential for a launch of rilonacept in the first half of 2021. We also plan to continue to execute across our entire portfolio in the second half of 2020 and beyond. As a reminder, in the fourth quarter alone, we expect data from our Phase II study of Mavri and GCA as well as our Phase I KPL-404, CD40 study. And we expect to initiate a dose-ranging Phase IIb study for Vixarelimab in prurigo nodularis. With that, I'd like to especially thank Nadine again for sharing a journey with all of us today, as well as Dr. Cremer for his insights into the pathophysiology and severity of recurrent pericarditis. I'll now hand it back to the operator to begin the Q&A portion of the call. Thank you. Operator?

[Operator Instructions] Our first question comes from Geoff Meacham with BofA.

This is Jason on for Geoff. Just a couple of quick questions. You mentioned the possibility of potentially expanding the addressable patient population outside of that 14,000 range, I know it's not going to be the primary focus, but can you talk a little bit about what you're doing on the regulatory front to maybe expand the indication? And then just in terms of looking at the regulatory time lines, could you be a little bit more specific on when you think you'll be able to submit and what that process will look like?

Yes. Maybe I'll hand it over to Q to start, and then John, you're free to jump in if you have any comments on the regulatory aspect.

Yes, happy to. So obviously, we will promote to whatever our label says. But I think we'll get this excited, and you saw this from the data John presented. The data from RHAPSODY are so compelling. The unmet need is real. And there is a patient population that does have these high-risk features, and I mentioned those are the tamponade, the fusion, the constriction. So even though that might be their first recurrence but if you have one of these high-risk features, we've heard from key opinion leaders, there is a desire to do more and help those patients more aggressively. So we haven't started label negotiations, obviously, with the FDA yet. So it's a little early to comment on exact indication statement and patient population that we will be able to promote to, but we feel we have a robust data package to engage with the FDA at the right time.

Anything to add, John?

Sure. Maybe one additional element about the treatment paradigm and the data as we engage in the regulatory process. So kind of speaking to a bit to how Dr. Cremer was talking about the therapeutic paradigm and the need for steroid sparing. So the way that you chose to study rilonacept in Phase II and also in the Phase III study, RHAPSODY, provided data which could inform a potential shift in the therapeutic paradigm of recurrent pericarditis is actually is a steroid-sparing agent. Specifically demonstrating the treatment and prevention of recurrent pericarditis, not only after steroids, but also demonstrating it's used potentially upstream, which could possibly obviate the need for initiating steroids in these patients for example, in the trial who were failing and had some colchicine. And so in that sense, it provides a robust data set as we engage with the regulatory authorities. But of course, as Q mentioned, we have not yet begun those conversations or understand exactly what the label will read.

Well, I guess, is it possible that you could have the broad label at first go around? I mean, is that in the realm of possibilities?

Well, I think the way we designed our data set was to describe the treatment and prevention of recurrent pericarditis. And then the next step is, of course, to have that regulatory conversation.

And our next question comes from Anupam Rama with JPMorgan.