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All right. Okay. Good afternoon. Welcome to the 2025 Jefferies Global Healthcare Conference. My name is Roger Song, one of the senior analysts covering SMid-cap biotech in the U.S. It is my pleasure to introduce our next presenting company, Kiniksa. And then we have the Chief Commercial Officer, Ross , and then Chief Medical Officer, John . They will do a no [corporate] presentation, and then we'll save some Q&A toward the end. Welcome.
Okay. Thank you very much, Roger. Thank you to the Jefferies team for hosting us here today. It's a pleasure to be here. My name is Ross Moat. I'm the Chief Commercial Officer at Kiniksa Pharmaceuticals. Today I will be providing both a corporate and a commercial update on Kiniksa. I'm joined here by my good colleague, Dr. John Paolini, our Chief Medical Officer, who will be providing a review of our clinical trial design for KPL-387, an exciting potential new development and a treatment option for recurrent pericarditis. Today, we will be providing forward-looking statements that are subject to risks and uncertainties, a full copy of which can be found either on this slide or under SEC filings on our corporate website. Kiniksa is a well-capitalized, growth-oriented company putting patients at the center of everything that we do.
We are aiming to address unmet needs by advancing novel therapies, particularly within cardiovascular indications. With ARCALYST, we have established our leadership in the recurrent pericarditis market. In Q1 at our earnings call, we were pleased to provide an increase to our net revenue guidance for 2025 of between $590 million and $605 million. We are also focused on advancing our clinical portfolio by developing KPL-387 in recurrent pericarditis. To that regard, our phase II/III, clinical design is expected to initiate in the middle of 2025, with data readout from the phase II portion of the study in the second half of 2026. Additionally, we are focused on maintaining a strong financial position.
In Q1 of 2025, with our ARCALYST revenue, we achieved profitability for the organization, and that added to our cash reserves, taking us to $268 million, which is important as it provides us optionality to invest in further value creation activities across the organization. Kiniksa has an innovative portfolio of both commercial and clinical stage assets. You may know that ARCALYST has been approved since 2021 in recurrent pericarditis and is also approved in two other rare conditions, in CAPS and in an ultra-rare condition called DIRA. Today, John will talk us through the KPL-387 clinical trial design in recurrent pericarditis. Before he does, I'll provide an update on the commercial side of the business with ARCALYST. Our team has driven robust growth, and we've delivered almost $1 billion in the four years since our launch as net revenue.
In fact, in Q1 of 2025, we delivered $137.8 million, which is a 75% year-over-year increase. The Q1 growth was driven by increases to both the active commercial patients on therapy as well as longer durations while on therapy. The active commercial patients were driven by an increase to the prescriber base, particularly from new prescribers, where in Q1 we had around 300 new prescribers of ARCALYST in recurrent pericarditis. In fact, that is one of the largest growths that we have had in any quarter since our launch. That took our total prescribers to more than 3,150 unique individual prescribers. Of that group, around 26% or 820 physicians have prescribed for two or more patients.
As I mentioned, the average total duration of therapy has also continued to grow since the time of our launch, most recently having gone from around 27 months to now around 30 months of an average treatment duration, which underscores a growing understanding that recurrent pericarditis is a chronic multi-year disease in most patients. Additionally, the other underlying commercial fundamentals also remain strong, whether that's the payer approval rate or patients' compliance to therapy. Our strong commercial performance in Q1 enabled us to increase our net revenue guidance for 2025 to between $590 million and $605 million. Our strategy is focused on continuing to drive future growth, whether that be through promoting to the breadth of the label, which is agnostic to the number of recurrences a patient has to have suffered before being treated with ARCALYST.
In fact, around 15% of all the patients prescribed ARCALYST are treated when they're on their first recurrence of the disease, with around 85% being on two or more recurrences. It is also crucial for us to continue to ensure physicians have a positive prescribing experience when prescribing ARCALYST. That means everything from knowing how to prescribe the drug, how to go through the prior authorization request, seeing their patient get access to therapy, and then also witnessing the effects while being on therapy aligned with what we saw in our clinical trials, which is a highly efficacious and well-tolerated drug. We are pleased with what we've achieved so far since our launch over the last four years. However, our Kiniksa team is even more excited about the future. In fact, at the end of 2024, we had reached around 13% penetration into the multiple recurrence target population.
That's the patients that have two or more recurrences in any given year. That speaks to the opportunity that we have ahead. Our team are very excited about reaching more and more patients and helping them during this suffering from this debilitating disease. With that, I'd like to hand over to Dr. John Paolini to provide an update on KPL-387 and the exciting potential new treatment option in recurrent pericarditis. John.
Thanks, Ross. As you can see, Ross and the entire commercial team have really performed exceptionally, placing the company on a robust trajectory and expanding our reach to help ever-increasing numbers of patients with recurrent pericarditis. Of course, we intend to maintain and extend our leadership in this space, building on that success. Our commitment to patients with this debilitating disease extends also to our pipeline development plans. Earlier this year, we announced a new program, KPL-387, our independently developed monoclonal antibody targeting the IL-1 signaling pathway. Today, we would like to share additional details of this program as it continues in its progress. On this slide, you can see some of the top-line data from the single ascending dose study, the single subcutaneous administration portion of that phase one study. This is a randomized double-blind placebo-controlled study, SAD and MAD, in approximately 112 healthy participants.
It evaluated the safety, tolerability, PK, PD, and immunogenicity of KPL-387. These data show that a single dose of KPL-387 at the 300 mg subcu dose level, which is shown in red, demonstrated sustained serum concentrations above the target concentration. That supports the profile of a monthly dosing paradigm. Data from this study were utilized to support the design of the upcoming phase II/III clinical trial in recurrent pericarditis. That is the slide that is shown here. Next slide. There we go. The phase II/III clinical trial will consist of three overlapping parts, which have been combined into a single protocol: the phase II dose focusing portion, the phase III pivotal portion, and two long-term extensions. The dose focusing portion of the study will enroll up to 80 patients randomized equally across four blinded dose levels to receive subcutaneously administered KPL-387 for 24 weeks.
Concomitant treatment with conventional oral therapies will then be weaned off to attain KPL-387 monotherapy. The primary efficacy endpoint is time to treatment response. Now, patients completing the dose focusing portion would then be eligible to enter a two-year long-term extension to provide for additional exposures and additional treatment duration. Following the dose focusing portion, the pivotal trial will begin. Up to 85 participants would be enrolled in a single-blind run-in period, during which KPL-387 would be initiated, and conventional oral therapies will again be weaned. Participants will be blinded to the duration of the run-in period. Subsequently, in the randomized withdrawal period, participants who respond to KPL-387 in the run-in period will then receive either continued KPL-387 or a placebo. This is an event-driven randomized withdrawal study with a primary efficacy endpoint of time to first adjudicated pericarditis recurrence.
Upon closure of the randomized withdrawal period, participants may be eligible to participate in the long-term extension. As always, ClinicalTrials.gov is a helpful resource for additional information and updates regarding our clinical programs. As Sandra mentioned in our previous meetings, our goal is to put this product into the hands of our commercial team as quickly as humanly possible and to bring this potential new treatment option to patients as soon as the 2028-2029 timeframe. With that, I'll turn it over to Ross for closing remarks. Ross.
Thank you, John. In summary, Kiniksa is well-positioned for both future success and value generation. You've heard from us today that we continue to be acutely focused on the ARCALYST commercial performance, and we were pleased to provide the net revenue guidance for this year of between $590-$605 million. We are also advancing at pace with our clinical portfolio, as you heard from John for KPL-387, expected to start in mid-2025. We are also incredibly focused on maintaining a strong financial profile with a growing cash balance, but optionality to invest in future value creation activities, whether that be via internal development or external business development. The team at Kiniksa could not be more excited about the future that we have ahead.
We'd like to thank you very much for those of you in the room today and listening online, and hand back to Roger to moderate the Q&A session. Thank you.
Thank you, Ross. Thank you, John. Yeah, that's a very comprehensive overview of the company. Yes, it's a very exciting journey for Kiniksa for the RP and then moving forward. Maybe we stick on the commercial side. Understanding the right now, the key focus is the multi-recurrence targeted population, and then the current penetration rate is about 13%. This is not like a real time, but kind of based on your market research. How should we think about the overall, what is the real potential for ARCALYST to penetrate into that targeted population? Another just interesting question is, those are the multi-recurrent at any given year, if they are not using ARCALYST, what they are using, and then what they are waiting for not to use the ARCALYST.
Yeah, great. Thank you for all those questions, Roger. Yeah, I think the best way of summing it up is that we're very excited and focused on the future. We think we have a huge potential left ahead, having been only 13% penetrated into the 14,000 patient population. You're right that we are focused on that 14,000 population, the two or more recurrences, but we're also promoting to the breadth of the label, which is the whole 40,000 patient population.
I think as physicians become more and more ingrained with ARCALYST and understand how to prescribe the drug, and they witness the benefits that their patient sees by being on treatment, we think that creates a positive halo effect, whether that's for individual prescribers to prescribe more when they identify their next patients, or through peer-to-peer education and encouraging other prescribers to diagnose and prescribe ARCALYST for their recurrent pericarditis patients. We think all those things are going very well. A lot of it is just down to education and awareness and the fact that there are many patients out there broadly spread around the U.S being looked after by many different cardiologists and everyone having a different experience.
I think what you've seen is one by one, we're switching on more and more physicians to this new wave and new way of how to treat the disease. People are becoming more aware that recurrent pericarditis is driven by interleukin-1 alpha and beta, and that ARCALYST is a targeted therapy for those cytokines and a targeted immunomodulator for them with the tremendous results that we've seen under the clinical trials. I think that all bodes well for the future. To your point around what are they waiting for, we think it's more education, more knowledge, more experiences in the community. There are a growing number of centers that are taking more and more of an interest now that there is a treatment available in pericardial diseases per se and kind of building more centers of excellence across the country.
We think that's very positive for the patient community to try to get a timely, accurate diagnosis and access through to targeted therapy when that's appropriate for the patients.
Got it. Yeah. I know you don't want to guide to the peak penetration rate or what's the future look like. Just out of curiosity, who are the patient population you think is not going to be addressed by the ARCALYST in terms of the multi-recurrent population? We're going to talk about the first recurrent in a minute. Just based on the profile and based on the feedback you're getting from physicians, do you think it really has a certain patient with multiple recurrence not eligible or should not, they're not going to be using the ARCALYST anyway, even with more education?
Yeah, it's a great question. I mean, I think the short answer is really not that we've seen so far. Obviously, it's up to individual physicians to decide what the right treatment path is for their patients and having a robust understanding of the patient's history and any underlying etiologies or complications that the patient may have. But the ARCALYST label is very broad. As I said earlier, agnostic to the number of flares and also agnostic to any other prior therapies that a patient has been on to try to control their disease. What we know is when patients have more and more flares, it precipitates longer disease and higher burden of the disease. The earlier these appropriate patients can get diagnosed and treated appropriately, the better for the patients and for their outcome and for their overall quality of life.
Got it. Okay. Yeah, that's a very good way to frame this. In terms of first recurrence, that's still not the current focus, but seems you are getting more traction than expected for the first recurrence population. Just in terms of the practice experience, do you see the difference between the first recurrence patient versus the multiple recurrence patient using ARCALYST? If so, how do you think ARCALYST can better serve the first recurrent patient with some different strategy or anything?
Yeah, we haven't seen any differences that we've observed so far. John can certainly speak around the resonance registry that we have to track real-world experience of the disease, which has come out with multiple data points that are interesting for the future to really understand this disease in the real-world setting. Other than that, no major differences between different patient populations is what we've seen. We think it makes sense for physicians to, when a drug first comes to the market and when you're really focusing on a paradigm shift and moving people away from previously having reached for corticosteroids because it was pretty much the only other available option after NSAIDs or colchicine have been utilized within these patients, it takes time to just create that new way of treating the disease.
I think it stands to reason that physicians often wait for the ideal type of patient, maybe someone that's had multiple recurrences, and they start there. To your point, over time, we've seen growth of the number of patients on the first recurrence of the disease, which I think speaks to that positive feedback loop, how physicians are getting on, how the treatment paradigm is really changing, and ARCALYST is being seen as a steroid-sparing therapy for patients. I think that all bodes very well for the future.
Got it. Okay. How do you think about the payer side? I know the label is covering the entire RP. Do you see the difference on the reimbursement side for the first recurrence versus multiple recurrence?
Yeah, generally not as a mainstay across the payer landscape. We have very good payer coverage, and that's greater than 90%. In fact, that's been the case ever since the time of launch, even when patients and physicians had to go through medical exceptions before policies were actually put into place. Now, of course, payers' policies have been in place for multiple years and have been iterated upon over time. Generally speaking, we've got a greater than 90% payer approval rate. We feel strongly that payers really understand the value proposition that ARCALYST brings to them and their patients and how it helps patients.
How about the duration on treatment? I know you probably have limited data for first recurrent versus multiple recurrent, but in terms of the patient, maybe they are less severe, they will be on treatment a bit shorter. How should we think about the duration on treatment between those two populations?
Yeah, I think some of that is certainly borne out in the literature showing that the more recurrences a patient has had, the more likely they are to have a longer duration of disease. In patients that have two or more recurrences, the median duration of the disease is around three years, and around a third of the patients are still suffering from recurrent pericarditis five years after the original index episode of the disease, and around a quarter of the patients still at eight years. We have been pleased to see that ARCALYST's duration of therapy has been growing since the time of launch, most recently as an average total duration of around 30 months. I think that speaks to, one, how patients are getting on on therapy, two, how physicians are understanding that this is a long-term chronic multi-year disease in the vast majority of patients.
Ultimately, that's how ARCALYST was also designed to be used throughout the natural history of the disease to control recurrent pericarditis, reduce the symptoms associated with the disease, and ultimately to prevent future recurrences. I think that's exactly what we're seeing, whether that's in the real-world evidence through the RESONANCE data set or if you look back at the clinical trials.
Just to clarify, for that duration on treatment, that's to include both the first recurrence and the multiple recurrence? That's also just the multiple recurrence.
That's great. That's the aggregated number across all recurrence numbers of patients, and it's the treatment time. There are patients when they stop therapy, we see around 45% of patients who come back onto therapy, generally within around an eight-week time period for most patients, and symptomology returns if the underlying autoinflammation has not resolved. If you add up all of the treatment periods from what we've seen so far, that's what adds up to around 30 months on average across all the cohorts.
Yeah, across all the cohorts, do you see the difference between the cohorts in terms of the duration on treatment? Because that's aggregated duration on treatment.
Yeah, and not that we've got robust data to share or provide in that regard. Some of that comes down to the fact that actually recording the number of flares a patient has had is also very difficult. If you ask a patient, they will tell you one thing. If you ask the physician, they will tell you something else for that same patient. Sometimes there's not a standard way of really understanding how many recurrences. It's a little bit tricky to get really robust data in that regard.
Got it. Yeah. I know every time I put you on the spotlight, and I want to ask a couple of questions to John as well. Thanks for Ross. This is a very important development for the next pipeline for the monthly dosing for KPL-387. The phase II, phase III seems they are very seamlessly switching or the transition from phase II to phase III. My question is, how are you going to determine the dose from phase II for those to the phase III dose? Maybe if I'm reading this correctly, it's one dose for phase III. Are you powered to see the difference in phase II in order to make a decision for phase III dose?
Right. No, that's a great question. Kind of on first principles, it's important to lay out that this is obviously a mechanism that at Kiniksa, we know a lot about and have a lot of experience with. Of course, we built upon our experience with RHAPSODY as a highly successful clinical trial in phase III supporting ARCALYST. We have a lot of knowledge of this pathway and how to kind of run these trials and extract useful information from them. What we've put forward in terms of this package, if you will, is a phase II dose-focusing portion of the study and then a phase III pivotal portion of the study, two long-term extensions, and they're kind of interconnected, if you will, and overlapping, but they're done as a single integrated protocol.
What that does is that allows us to move this program forward very quickly, which is why we say that this dose-focusing portion starts in the mid-year this year in terms of how we then use that information. These are all actively flaring patients who are coming in despite their background therapies and KPL-387 is layered on. The primary efficacy endpoint is certainly time to treatment response, but there is a wealth of information that you gather across these four different dose levels that help us understand if you anchor on the monthly dose, is the first principles, is the monthly dose sufficient? If you give more drug, do you get additional efficacy? Or in fact, is that sufficient?
If you remove or give less drug, do you end up with certain weaknesses in certain of the endpoints that then help you understand or build the case to the agency that you have a minimally effective dose level? Once you've done that, we will use the totality of that information going forward. I think that's what we can say about that. What I will also say is that once we've kind of completed what we've needed to learn from that phase II portion, we can then start the phase III portion of the trial, even though the phase II study will continue into the long-term extension, the dose-focusing portion will continue into the long-term extension. That concurrent activity is again a way to pick up speed.
The idea is to take forward one dose level into the pivotal program, and then that is what would move forward to registration.
Got it. And then given this is based on totality of the data, we should not just expect you will have to see statistical difference among those four doses in order to make the phase III decision. Is that right?
Yeah, no, that's a great question. By speaking to the totality of the data, if you will, the purpose of the study is to collect information at these different dose levels such that we can build our PK/PD understanding and explain that to the agency. There's no necessarily implied comparison across or explicit comparison across the different dose levels, but rather it's more, as I mentioned, understanding that if you anchor on the concept of monthly dosing, then you ask the question, if you give more drug than what is on that anchor dose, if you do not see additional efficacy, and if you see less efficacy, if you get underneath that, that's the critical element.
What you see in our PK/PD modeling, which is on our corporate website, is that from that target concentration, we actually cover orders of magnitude above and below that target concentration, which allows us to generate an enormous amount of information.
Excellent. Great. Maybe just one last minute in terms of the financial position and then where you are in terms of the bottom line, and then you give us the revenue guidance. I believe you have some operating OpEx guidance as well. Just what's the financial position, and then you can let us know.
Yeah, thank you, Roger. We've just shared that we aim to be cash flow positive on an annual basis. As I mentioned in Q1 of this year, we were profitable thanks to the growing revenues of ARCALYST. We have cash reserves as of the end of Q1 of around $268 million. We believe that that helps to provide us optionality for future investments. We're an organization that is very focused on growth and the ability to invest in future value generation.
Excellent. All right. Thank you for being with us this afternoon, and thank you everyone for listening. Thank you.
Thank you so much.
Thank you.