Welcome, everyone, to Jefferies Lending Healthcare Conference 2025. My name is Roger Song, one of the senior analysts covering biotech in the U.S. It is my pleasure to host my section, the next session, with Kiniksa. We have Chief Commercial Officer Ross Moat and then Chief Medical Officer John Paolini. They will have a corporate presentation, a high-level overview of the company, about 20 minutes, and then we can leave some time for Q&A. Okay, Ross.
Okay, thank you, Roger. Thank you very much to the Jefferies team for hosting us today. It's a pleasure to be here. John and I are going to be providing an overview of Kiniksa and where we are in terms of both our commercial progress and the robust progress that we've had since our launch, as well as the activity across our pipeline. John is our Chief Medical Officer, and I'm the Chief Corporate and Commercial Officer at Kiniksa. Before we go any further forward, I just want to share with you that we will be providing forward-looking statements today, which are subject to risks and uncertainties, a copy of which can be found on this slide, as well as on our corporate website under SEC filings.
Kiniksa is a well-capitalized, growth-oriented organization focused on addressing unmet needs by bringing novel therapies to patients who are suffering from debilitating diseases. On the commercial side of the business with ARCALYST in recurrent pericarditis, we have established our leadership within the recurrent pericarditis market. In fact, in the four and a half years since the approval by the FDA in recurrent pericarditis, we've delivered more than $1 billion in net product revenue. We have continued potential ahead for further growth. We're only 15% penetrated into the multiple recurrence population, which is the population that is suffering from two or more recurrences, as well as having a further upside in patients that are on their first recurrence, so earlier on in the disease course, which is an additional 26,000 patients on top of the 14,000 patients that suffer multiple recurrences.
At our Q3 earnings call recently, we increased our net revenue guidance for full year 2025 to between $670 million and $675 million. Additionally, on the portfolio side of our business, we're advancing the clinical portfolio, particularly with KPL-387 in recurrent pericarditis, where just in October, the FDA granted the orphan drug designation for the drug for the treatment of pericarditis. We have initiated the phase 2/3 development program, and we are expecting the phase II dose-focusing portion of the study to read out in the second half of 2026. Furthermore, we're undergoing IND-enabling activities for KPL-1161, which is an FC-modified, potentially quarterly interleukin-1 alpha and beta inhibitor that could have multiple uses in different disease areas. Additionally, we are focusing on maintaining our strong financial position. At the Q3 earnings, we announced we had more than $350 million in cash reserves.
Through the growing revenues of ARCALYST, we have the optionality to invest further in additional value creation activities across the organization. We have driven substantial growth in ARCALYST sales, and that's been driven by the expanded adoption of interleukin-1 alpha and beta inhibition in recurrent pericarditis. At Q3, we delivered $180.9 million in net product revenue, which is a 61% year-over-year increase versus the same quarter of 2024. If we look at which patients are being prescribed ARCALYST in recurrent pericarditis, we see that around 80% of the patients that are prescribed ARCALYST are on their two or more recurrences.
That also means that around 20% of the patients are now being prescribed ARCALYST earlier on in the disease course on only their first recurrence of recurrent pericarditis, which, as a reminder, the breadth of the label is for the treatment of recurrent pericarditis, which encompasses all of those patients within the 40,000 patient population. That 20% on the first recurrence is up from around 15% at the same time of last year, which we believe bodes well for health physicians who are transitioning their treatment for this patient population and moving more towards interleukin-1 alpha and beta inhibition to address this very debilitating disease. As I mentioned earlier, we have significant opportunity ahead as we're only around 15% penetrated into the market of two-plus recurrences. We have continued our commercial performance since launch and increased the number of active commercial patients on treatment.
As I mentioned earlier, we increased our revenue guidance to $670 million-$675 million, and we continue to have a robust strategy for how to address this market. We are focused on promoting to the full scope of the label for recurrent pericarditis, which is agnostic to the number of flares a patient must have suffered before being eligible for treatment with ARCALYST. We're also very focused on making sure that physicians have a positive prescribing experience. That means they know exactly how to prescribe ARCALYST, how to go through the prior authorization to get access through to the drug, that they are confident that their patients will get access to ARCALYST, and that they will experience the type of results in the real world that we saw in the clinical studies, which resulted in a highly efficacious and well-tolerated treatment.
By ensuring that physicians have a very positive experience in prescribing ARCALYST, we believe that will also build momentum for repeat prescribing, as well as peer-to-peer education on this changing landscape of how to treat the disease. We're also very focused on making sure that we create an efficient network of care across the U.S., with the building of regional pericardial disease centers, which at the time of our launch were in a very limited number, around two key centers in the U.S. Under an initiative and a collaboration with the American Heart Association called Addressing Recurrent Pericarditis, those centers have grown, and there are now around 18 centers in the U.S. providing focused specialized care for pericardial diseases per se.
We are driving the recognition of recurrent pericarditis as a chronic multi-year disease and one that needs to be treated throughout the course of the disease with the utilization of interleukin-1 alpha and beta inhibition to appropriately address the debilitating disease. As I transition to our pipeline program, focusing on KPL-387, this drug aims to address the key patient needs and expand the adoption of interleukin-1 alpha and beta within the market. Based on our research within this market, the vast majority of surveyed healthcare professionals believe that this target product profile of KPL-387 would do exactly that and expand the market for interleukin-1 alpha and beta. As a reminder, that target product profile is a highly efficacious, well-tolerated drug for recurrent pericarditis that is a monthly auto-injector format.
If you look on the patient side, around 75% of all patients believe that the introduction of KPL-387 with that target product profile, that would be their first choice above available commercial and current investigational therapies. On the healthcare professional side, greater than 90% of healthcare professionals reported that they would have a very high likelihood of prescribing KPL-387 for both new patients, as well as being receptive to switching existing patients if it was requested by the patient. As you can hear, we are very excited about the potential that we have for ARCALYST in the years ahead, with substantial opportunity to grow ARCALYST and address many, many more patients with recurrent pericarditis, as well as being excited by KPL-387 to add to the treatment options for recurrent pericarditis patients for the future. With that, I'd like to hand over to Dr.
John Paolini, who will talk us through the KPL-387 clinical trial program in more detail. Thank you, John.
Thank you, Ross. Good afternoon, everyone. As you can see, Ross and the entire commercial team have continued to deliver strong performance and positioning Kiniksa for future value creation. Of course, we intend to maintain and extend that leadership in this space. Our commitment to patients with this debilitating disease extends also to our pipeline programs. Earlier this year, we announced the KPL-387 development program, and today we'd like to share some additional details of that program as it progresses forward. The IL-1 pathway is clearly a pathway that Kiniksa knows very well. The data to date have demonstrated that inhibition of both IL-1 alpha and IL-1 beta is critical for comprehensively blocking the disease mechanism. We've therefore doubled down on this concept of dual inhibition as we've considered the independently developed KPL-387 program.
As a fully human IgG2 monoclonal antibody antagonist, which is binding to the IL-1 receptor subunit IL-1R1, KPL-387 inhibits directly both IL-1 alpha and IL-1 beta signaling. Let's break that down a bit. In blocking downstream IL-1 beta signaling, there is inhibition of the cascade amplification system that is responsible for systemic inflammation. Importantly, blocking upstream IL-1 alpha signaling also prevents localized inflammation that is in the pericardium. In addressing both the systemic as well as the localized inflammatory pathways, we believe that KPL-387 covers the pharmacology necessary to support a highly efficacious therapy. KPL-387 is designed to enable once-monthly dosing in a single subcutaneous injection in a liquid formulation in an auto-injector, potentially providing a new therapeutic option that addresses the needs for patients suffering from recurrent pericarditis, as Ross has mentioned.
The phase I data that we've previously shown demonstrate that the single-dose KPL-387 pharmacokinetics at the 300 mg subcutaneous dose level provided sustained serum concentrations above the target concentration, supporting the monthly dosing paradigm and the design of the late-stage clinical programs. Now shown here. As you would expect, in designing the integrated KPL-387 development program, we've drawn on our extensive trial design experience from RHAPSODY, which was our highly successful phase III program, which supported the supplemental BLA of ARCALYST in recurrent pericarditis in 2021. Earlier this year, as Ross mentioned, we initiated the streamlined phase 2/3 clinical trial program, which, as a reminder, consists of three overlapping parts combined into a single protocol. There's the phase II dose-focusing portion, the phase III pivotal portion, and then long-term extensions.
The core component of the phase III is the phase III study, which is shown there in red, which we believe is pivotal to support registration. The dose-focusing portion is underway, and we are on track for delivering data and reporting those data in the second half of next year. Additionally, in order to provide a complete data set at the time of product launch in a range of different clinical scenarios, we also plan to conduct a supplemental transition to KPL-387 dosing and administration study, which, while not obligatory to the future BLA package, is designed to provide supplemental information on the efficacy and safety of dosing regimens used to transition patients from standard therapies, including NSAIDs, colchicine, corticosteroids, IL-1 pathway inhibitors such as anakinra and ARCALYST, to KPL-387 monotherapy.
As we've mentioned in prior meetings, KPL-387 could provide an important advancement in the treatment options available for patients with recurrent pericarditis. Our goal is to put this product into the hands of the commercial team as quickly as humanly possible and to bring this to patients as soon as the 2028-2029 timeframe. With that, I'll hand it over to Ross for concluding remarks. Thank you so much.
Thank you, John.
Thank you.
Just to conclude our presentation, hopefully you've heard from us today that Kiniksa is well-positioned for future success and further value creation. We are very focused on ensuring that we continue to maximize the current commercial opportunity with ARCALYST in recurrent pericarditis, and we guided to $670 million-$675 million for the full year 2025. We are also very focused on advancing the clinical portfolio, as you've heard today, with KPL-387, which is in the phase 2/3 clinical study, with data expected from the dose-focusing portion of the phase II study in the second half of next year, as well as undergoing the IND-enabling activities for KPL-1161 as a quarterly interleukin-1 alpha beta inhibitor. We are also very focused on maintaining our strong financial profile.
At last reported with $352 million cash reserves, as well as the growing ARCALYST franchise, we expect that we have the optionality to continue to invest in further value creation opportunities across the organization. I'd like to thank you very much for joining us here in the room today, as well as online, and thank you to Roger. We will stop and hand over to you to moderate the Q&A session. Thank you.
Thank you.
Okay. All right. Thank you for the presentation. And obviously, ARCALYST is off a very good long trajectory and then sales trajectory. And then also we have the new pipeline coming up for the monthly and even quarterly for the interleukin-1. So maybe first set of questions still focus on the sales for the ARCALYST. Start with a very near term, right? So we are in 4Q right now, and then you obviously give us the guidance for 2025 and then into 2026. How should we think about, because you have been being raised every quarter, right? So how should we think about 4Q performance given we are halfway through? And then how should we expect from the new year guidance early next year?
Yeah, thank you very much, Roger. We provided the guidance on the Q3 earnings call of $670 million-$675 million, trying to be as accurate as we possibly can be with our forecasting and thinking through what we know about the trajectory since the launch and the trajectory of this year so far. We feel somewhat confident within the guidance range that we provided. We think that there is substantial growth left within this opportunity. We see how kind of Q4 plays out. There is always a lot of uncertainties going into the end of the year. We have always said, for example, gross to net is often a little bit higher in Q1, lower in Q2 and Q3, and kind of pops up again a little bit in Q4.
We've never seen substantial swings in either direction, but there are some of those factors that come into Q4. We feel kind of optimistic and pleased with the trajectory that we're on. I think more importantly, we are just very focused on the opportunity that we have ahead, and we're making good progress. We want to serve many, many more patients that just have this unmet need in recurrent pericarditis and are really suffering from what's a very debilitating disease for many patients. The opportunity therefore is to continue to progress and help those patients in time to come is very significant.
Got it. Okay. Yeah, that makes sense. Obviously we'll look forward to 4Q and then the new year guidance. I think the new year guidance potentially can be coming before the 4Q kind of the readout. I think historically you were giving us the guidance in the early year.
Yeah, thank you. We haven't said exactly when we'll provide the full year 2026 guidance. We think about what the opportune time is as we kind of see how we progress through the rest of this year.
Sure, that's fair. In terms of the, you have a targeted population as a second plus or two plus recurrence, and then you also penetrate into the first recurrence. Maybe just focus on the current focus, the target population with the two and the plus recurrence population. Understanding every metric is going up quite well, penetration rate and the compliance rate, everything. Knowing one dynamic is new patient versus the stopping patient. I think the stats there is quite steady. Is there any strategy or tactics you can further improve this patient stay on treatment and maybe increase those patient kind of retreatment after first dose?
Yeah, it's a great question. Thank you, Roger. One thing that we're very focused on educating on in the healthcare professional community is the natural history of the disease and the duration of the disease, which in one major piece of work, it showed that the median duration for patients that are on two or more recurrences of the disease is three years. We're still a third of the patients suffering from the disease after five years, and a quarter of the patients still suffering the disease after eight years, which is actually when that time point of that particular piece of work kind of finished. We don't know what the average is, but what we do know is for these patients on two or more recurrences, this is a long chronic multi-year disease for the vast majority of them.
We think the increase in education around that and the knowledge that ARCALYST is designed to be treated throughout the course of the disease is very important. We have seen the duration of ARCALYST grow since the time of launch, most recently reported around 32 months on average. We're pleased about that. Generally, patients are quite compliant on therapy and do well on therapy. We're pleased with that. In terms of kind of new patients coming in, I mean, in Q3, we actually saw the highest number of new prescribers prescribe ARCALYST for the first time for recurrent pericarditis in any quarter since our launch four and a half years ago, which I think just again underscores the opportunity that there is out there. While we haven't provided exact patient numbers and so on, the fact that the prescriber count is growing.
About 50% of all new patients prescribed ARCALYST in a given quarter come from new prescribers, and about 50% are those repeat prescribers that are prescribed the second, third, fourth, fifth, and so on patients. It's a pretty healthy split. Patients that suffer recurrent pericarditis go in to see any one of the 30,000-40,000 healthcare professionals across the U.S. We have had around 3,850 or so prescribe ARCALYST to date, which again, I think speaks to the opportunity that we have to continue the education and the awareness of recurrent pericarditis and ARCALYST and the need to go and serve more patients.
Got it. Okay. As we know, you also penetrate into the first recurrence population, right? We mostly treat that as the upside case, seems also steady growth. Do you think at some point, maybe we'll talk about the monthly, do you think at some point this will become another major driver of the growth story in the more near term or the midterm long term?
Yeah, I think it's been a good trajectory to see. As I say, it's around 20% of all ARCALYST prescribing. Now, when you ask the patients of how many flares they've had at the time of ARCALYST being prescribed for them, around 20% of our patients said that they were on the first recurrence and around 80% said on two or more recurrences. That 20% has grown over time. We think as physicians get more comfortable and confident in how to prescribe this drug and see the type of effects that it has to their patients, that's gravitated towards earlier line use in terms of the flare number.
On top of that, then also we saw, for example, the American College of Cardiology Clinical Concise Guidance publication several months ago now, pushing interleukin-1 alpha beta ahead of the utilization of corticosteroids in those patients with multiple recurrences, which again is another factor that plays into how physicians are treating this disease and the momentum that we're on in the new way and the new wave ultimately of treating the disease.
Yeah, makes sense. Segue to the monthly dosing. First of all, what is the real main need that you try to address with the monthly dosing outside of just convenience? Is that also coming from your market research or the feedback from the field, say this monthly, yes, we want to use that in certain population, maybe including the first recurrence population?
Ross, actually, you have some initial data about what is appealing to physicians and patients, and then maybe I can talk a little bit about the program itself and how that meets that.
Sure. Thank you. Thanks for the question. Yes, we're excited about KPL-387 and the potential that that has. With the market research that we shared on one of our corporate slides as well, patients are generally saying that this target product profile is something that they would choose for how to treat their recurrent pericarditis. Greater than 75% of patients labeled that target product profile of KPL-387 as being the choice that they would make when treating the disease. To an even greater extent, physicians said that this would be something that they would likely prescribe as their treatment choice for recurrent pericarditis as well. The ability to potentially have a monthly interleukin-1 alpha beta that's hopefully well tolerated and has high efficacy could lend a significant help to how to help these patients in the community.
Got it. Yeah. Maybe John, you can talk about what you want to see for the phase 2/3 the phase II portion, and then what's the ultimate label you're looking for?
Sure. The phase II program is a dose-focusing study. We're thinking about monthly dosing. The purpose of that study is to really look at the monthly dose and how that performs in the flaring patient population and look at dose levels above and below and understand whether more drug or confirm whether more drug does not provide more value and to then demonstrate how lower doses illustrate the PK/PD responsiveness to affirm the dose level that we would carry forward into phase II. It's important to realize that there's kind of an initial treatment response that you see when you initiate therapy in an add-on paradigm. Ultimately, with a six-month duration of therapy, it enables the removal of oral ancillary pharmacology and focus down on KPL-387 as a monotherapy to maintain disease control.
This is really doubling down on that basic concept that I mentioned in the preparatory marks about the importance of blocking both IL-1 alpha and IL-1 beta for comprehensive disease control. Moving forward into the phase III portion, which is the pivotal portion, it is a classic randomized withdrawal program with some innovations, of course, to keep modern, to think forward into what the practice of cardiology, specifically to recurrent pericarditis, will look like as we go forward into the 2030s.
Excellent. Okay. I think we have this amount of time that we can do this, but really appreciate the time together. We look forward to the new year for the ARCALYST and then the pipeline development.
Thank you so much.
Thank you, everyone.
Thanks.