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

Okay. Good afternoon, everyone. I'm Paul Choi, the SMid cap biotechnology analyst here at Goldman Sachs. And we'll continue with our next session, which is Kiniksa Pharmaceuticals. I'm very pleased to host from the management team here today, Chairman and CEO, Sanj Patel. We're also joined by the Chief Medical Officer, John Paolini, and as well as Qasim Rizvi, who is the Chief Commercial Officer. I believe we also have Eben Tessari on the line as well here. As with past sessions, I'll kick it off with some intro comments and then turn it over to Sanj for some opening remarks. We'll proceed then with the Q&A portion of the session. And if along the way, any clients who are listening have questions, please feel free to submit them via the Goldman Sachs research portal and time permitting at the end, we'll read them out loud. Alternatively, investors can send questions to me directly as well. And so with that, we'll kick off the session. And Sanj, if you want to kick it off here with any opening remarks?

Thanks, Paul. Good afternoon, and thanks also to Goldman Sachs for hosting the call today. Please note that we will be making forward-looking statements today that are subject to both risks and uncertainties. A review of these statements and risk factors are found under the heading of Risk Factors in our SEC filings. As Paul mentioned, I'm joined by John Paolini, our Chief Medical Officer; Qasim Q. Rizvi, our Chief Commercial Officer; and Eben Tessari, Chief Business Officer. By way of opening comments, with the help of an absolutely brilliant team, we are advancing a pipeline of immune-modulated clinical-stage product candidates at Kiniksa. We've had a very busy and productive first half of 2020. We recently announced encouraging data from both our Vixarelimab and mavrilimumab programs, and I'll refer to them now as Vixa and Mavri for everyone's sake on this call. Importantly, all of our private program time lines have remained on track despite the pandemic crisis. The second half of the year is also catalyst-filled. We announced in the press release just yesterday the data from our pivotal Phase III study with rilonacept in recurrent pericarditis is expected in Q3 of this year. Importantly, we're also preparing for the commercialization of rilonacept in recurrent pericarditis, and we have a crack commercial team under Q's leadership. We have Phase II data from our Global Phase II study of Mavri in giant cell arteritis in Q4 of this year, and we have data from a single ascending dose Phase I study with our CD40 program, KPL-404. And after recently receiving IND clearance, we plan to initiate a Phase II -- Phase III study of Mavri in severe COVID-19 pneumonia and hyper inflammation. And we're also planning a Phase IIb dose-ranging study for Vixa in prurigo nodularis. So as you can see, we've got a lot ahead of us. And happy to turn it back to you, Paul, for questions.

That sounds great, Sanj. Thanks for the overview. Maybe we'll start with this, which is a question I've been asking all management teams. We're certainly operating in a very unusual environment for biotech across the industry here. So could you maybe talk about the impact from COVID on your clinical trial time lines? Is there anything happening there that you'd want to call out and do you expect any other headwinds, either from a clinical operation perspective or other perspective on your plans here?

Of course, Paul. And as I mentioned earlier, all of our program time lines do remain on track despite the pandemic. We, of course, continue to monitor our daily operations and our time lines very carefully, particularly as the pandemic evolves. I have to say the health and safety of Kiniksa's employees as well as the patients and all the people participating and operating the company's trials are, of course, absolute utmost important to us. But as I said at the beginning, in our release just yesterday, COVID-19 hasn't impacted our time lines for clinical data in 2020. In fact, we did say in the release that we -- following the receipt of the breakthrough therapy designation and a successful type B meeting with the U.S. FDA for our rilonacept program, we were able to accelerate our development time line and actually now expect pivotal Phase III data in the third quarter of this year. Much is the same with our Mavri program with giant cell arteritis. As I mentioned, that data is expected in Q4 this year. And the KPL-404 CD40 program is still expected in Q4 this year also. So we're monitoring it very carefully. We're obviously taking all the steps to protect our employees and everybody involved in our trials, but we are, definitely, at the moment, on track.

That's great to hear, Sanj. Thanks for that. Maybe we'll start talking about some of the specific assets in your pipeline. And we'll talk perhaps about starting with recurrent pericarditis. And as we think about the clinical hurdle rate here, typically, AIRTRIP is thrown out there as the clinical bar here in RP. So can you maybe frame for us, given that, that data is out there, what would you consider a win here from your perspective for the Phase III RHAPSODY trial, that is testing ARCALYST. And then I had a follow-up question on that as well.

Yes. I'll ask Q to jump in here because obviously he's very much involved in that program clinically as he's getting ready for the commercialization. And so, Q, do you want to jump in and I can just follow-up towards the end?

Yes. Absolutely happy to. Thanks, Sanj. So Paul, I think the first point I'd like to make is that there currently are no FDA-approved therapies for recurrent pericarditis, and I think there's a tremendous opportunity there for us to fill that void. So if rilonacept were to be approved, it would be the first and only treatment to have kind of undergone kind of this rigorous regulatory review, both for efficacy and safety in the recurrent pericarditis. Now you mentioned AIRTRIP, I think it's really important to put AIRTRIP into perspective. And you'll recall that it was a single academic site study with 3 Italian referrals. It enrolled a total of 21 corticosteroid-dependent patients, with only of 11 them actually being randomized to anakinra. So I think it's critically important for us to be very careful in terms of comparing data from AIRTRIP with RHAPSODY. And it becomes really challenging, just given the difference in the patient populations and actual differences in the study design. You'll recall that RHAPSODY is a large global Phase III label-enabling study in a much broader patient population, not just corticosteroid dependent. And the study was specifically designed to generate data on what we believe are 4 of the most important areas of unmet need, those being the clinical resolution of the acute episode, prevention of future episodes, the need for a steroid-sparing treatment option as well as improvement in quality of life and with RHAPSODY, which should be a confirmatory study to our Phase II pilot study, which already has demonstrated rilonacept's ability to address all these 4 areas of unmet needs, you'll recall that the pilot study showed a rapid and sustained reduction in pain and inflammation after the first dose. And actually, that was maintained throughout the study. In the pilot study, we were also able to show that there was a decrease in the annualized incidence of pericarditis across all the cohorts and patient types. There was approximately 4 episodes per year prior to enrollment in our pilot study, and that was decreased to less than then 1 episode per year. And we also saw that all patients on corticosteroids either stopped or were tapered off their steroids during the extension period. And then finally, we saw a meaningful improvement in the quality of life for these patients. So honestly, I think, bottom line, we believe that rilonacept is going to set the bar for patients in recurrent pericarditis, given the robustness of the Phase II study by offering a well-tolerated, weekly subcutaneous dosing regimen, plus what we believe will be a compelling value proposition.

Great. So maybe to follow-up on that, Q. As you think about what other features would make it preferred over anakinra here, you talked a little bit about the dosing schedule. But could you maybe also talk or elaborate on any early stage commercial plans that you may have for a launch here into the recurrent pericarditis market for ARCALYST, what are you going to emphasize, I guess, in terms of your go-to-market strategy? And is there a particular physician base that you're going to target as sort of the low-hanging fruit here?

Q, maybe I'll just jump in, sort of, with a broad comment on the opportunity, and maybe you can jump in with some more of the details. But I think that's a good question, Paul. First of all, what we like about the commercial opportunity for rilonacept in recurrent pericarditis is that requires a limited commercial infrastructure. And we tend to have a specialty cardiology sales force of approximately only 30 reps, and they'll call on the high-volume specialists. They'll also be supported by our existing MSL team, Medical Science Liaison team, as well as highly efficient additional marketing efforts. So maybe, Q, if you could just go over some of those details in terms of the evidence that we're generating so far.

Yes. Absolutely, Sanj. And Paul, I think the best way to think of this launch and at least, how we're thinking about it, it's a rare disease launch, which means that the patient acquisition and retention is absolutely critical. So that's where most of our efforts are focused. So we're developing tactics and programs to try to help with broad uptake and adoption of rilonacept as well as ensuring a positive experience for our customers, including the patient. So internally, we're starting to build core capabilities around 3 kind of big areas. First being in terms of the strategic insights and commercial operations. We really want to make sure that we are rightsizing for the opportunity that was building the platforms and the technology to help us effectively communicate with our customers. Second area that we're building capabilities around is payers and reimbursement value and access. We're paying specific attention to patient services, distribution, payer and channel management because they will be critical for our success. And the third area that we're working on is really building a strong science-driven sales and marketing organization. So that's kind of where the focus has been internally. Externally, we're focused on building credible relationships with our key stakeholders, and we've already engaged with payers, physicians and patient advocacy groups. And we're starting to generate data to further support the unmet need and the burden of illness in recurrent pericarditis, and we're starting to increase that awareness amongst all our stakeholders that I mentioned earlier, payers, physicians and advocacy groups. So those are some of the things that we've been doing on the kind of the sales and marketing front. Specifically, as Sanj mentioned, on the sales side, we intend to have a very focused and targeted specialty cardiology sales force. We believe that with approximately 30 reps calling on the high-volume accounts and the high-volume prescribers within those accounts, that includes both cardiologists and rheumatologists. We primarily will focus on the cardiologists. And with 30 reps, we're pretty confident we can cover about 75% of the target patient population. And that's primarily because most of that opportunity is concentrated within about 800 accounts. So I think with 30 reps, that's a fairly reasonable volume of work for that sales force. And then as Sanj mentioned, the mission of the sales team is going to be supported with an MSL team. We already have that in place as well as a very efficient digital strategy and nonpersonal promotional marketing efforts. So we're kind of taking a very focused and targeted rare disease approach to this launch. And while our strategy is to drive broad adoption, it is important to keep in mind that the initial uptake can be slower. And I wanted to highlight maybe a couple of reasons why that might be the case. The time required sometimes to get payer coverage and payer policies, finalized and in place and formulary access, it can take a little bit longer than anticipated. So that's an important factor there. But also the nature of recurrent pericarditis is a flaring disease, means that patients will likely not initiate therapy until they actually have an actual flare. So there's unlikely to be this bolus of patients on day 1 that can rapidly be -- and quickly converted to rilonacept. And then as we're talking more with physicians, we're starting to appreciate that there's a range of comfort amongst the cardiologists in terms of which patients that are likely to start on therapy first and how long they would keep them on therapy. Once they've gained that initial experience and that initial experience might be with the more severe or difficult-to-treat patient. Once they've gained that initial experience, we're confident that they'll broaden the pool of their current pericarditis patients. And then just maybe one final comment on the cardiology space is that it's a limited amount of experience initiating patients on biologics within the broader cardiology community. Clearly, there are certain centers of excellence that are very comfortable, but you're talking more broadly about the cardiologists across the U.S. So there's going to be a certain amount of training required and a number of kind of cycles of sales reps calling on them to really get them comfortable to incorporate rilonacept in to their regular treatment algorithms. So I'll stop there and maybe hand it back to Sanj. Sanj, if you've got any other comments?

No, I think you covered it very well, Q. I think the only other thing I'd add to that is that another important metric is the duration of therapy. And in fact, based on our market research, we think that patients could be treated for 6 to 9 months initially. And in fact, up to at least 12 months longer term. In fact, several physicians have said that they expect to treat patients for even longer. So this is a chronic therapy, in essence. So that's -- and that data set is very much in line with the data set we'll be providing to the regulators as part of our sBLA filing. So I think all in all, we're very excited about the commercial opportunity. Just a word on price because I get asked that question all the time. We expect this to be in line with the high unmet need of this disease and the gross price for rilonacept, also known as ARCALYST, in CAPS, which obviously is an approved product with indication for CAPS at the moment, is $20,000 a month based on the weekly administration. So we feel very excited about this opportunity.

Great. Yes. I was just going to say to add on to what you said, Sanj, I thought Q was going to talk about the longer-term safety record since ARCALYST has been on the market for a while now with CAPS, as you indicated here. And so that's something that could potentially be supplementary in terms of the safety database that you're talking about. I did want to maybe just follow-up a little bit in terms of payer coverage. Since it is approved for CAPS there. Could you maybe elaborate on why that would take a little bit more time since it is a bit of a commercial -- it is already a commercial-stage product, albeit for a different indication?

Yes, we don't anticipate it taking any longer than normal therapies would take, but it's not something which payers do overnight, even for disease in areas with the highest of unmet need. So it's just really more of a watch out for us, that means it's something we're paying acute attention to, making sure we're engaging the payers, and they understand the disease, the burden of the disease and the value proposition of rilonacept in this space. So I bring it up just to kind of highlight the fact that it is a potential barrier that we are acutely aware of and are going to be prepared to address.

Got it. So maybe just because it's a topic du jour, given the environment we're operating in with respect to COVID here. Could you maybe talk a little bit about the early data we've seen from Mavri in severe COVID patients with respiratory complications? And how you're thinking about potential development and the opportunity there? Because this is something I suspect a lot of people did not have it in their models.

Yes, sure. So to start, the data so far from our treatment protocol in Mavri in patients with severe COVID-19, certainly are very encouraging. You'll recall we started with a treatment protocol in Italy with initially 13 patients, and we had very encouraging data then. But most recently, we had data with a 28-day follow-up with a matched control of about 26 patients. And again, that data was very encouraging. Then when you combine that with our own clinical collaboration with Kite Gilead in CAR T cytokine storm as well as our Global Phase II program in giant cell arteritis, I think what you're seeing here is the potential broad utility of Mavri, and that's how we think about value. We want to create value, the most value to our programs. So we think that's a good thing for both patients as well as for the overall value of the program. Perhaps, John, you can provide a few of the study details and more of the deals of the data. But I think overall, as far as the opportunity, we see it as a broader utility and a broader potential for the program and hopefully, an approved label via our now approved IND for our own Phase II, Phase III in COVID-19 with Mavri.

Well, thank you, Sanj, and good afternoon, Paul. So this treatment protocol was a prospective interventional single active arm and single center pilot experience in Italy. Specifically, there were 13 non-mechanically ventilated patients with severe COVID-19 pneumonia and hyperinflammation, and they were treated with a single intravenous dose of mavrilimumab when they were admitted to the hospital. And so as a control group, there are 26 contemporaneous non-mechanically ventilated patients with similar baseline characteristics. And of course, all of these patients receive standard-of-care therapy, including Proteus inhibitors and antiviral therapies as was being used in Italy at the time. So as Sanj mentioned, the 28-day outcomes data from the protocol were presented by Professor Dagna over the weekend at the ULR meeting. And these data, which you presented, are consistent with the 14-day data that we announced earlier which showed improved and earlier clinical outcomes for mavrilimumab treated patients, compared to the contemporaneous controls, and I'll take you through some examples. First, the severity of this disease in this population was illustrated by the fact that just over 1/4 of the control group patients died by day 28. In contrast, no mavrilimumab treated patients died. A bit over 1/3 of the control group patients progressed to mechanical ventilation or died by day 28, whereas only 1 mavrilimumab treated patient received mechanical ventilation. All of the mavrilimumab treated patients attained clinical improvement endpoint, which is an improvement of greater than 2 categories on the 7 point World Health Organization scale for the assessment of clinical status by day 28 versus 2/3 of the control group patients. And in fact, the time to that improvement was faster, 8 days on mavrilimumab versus 19 days in controls. And also fever resolved in 91% of the mavrilimumab treated patients by day 14 compared to 61% of control group patients. And again, that resolution was faster in Mavri treated patients 1 day versus 7 days. And ultimately, mavrilimumab was well tolerated in all patients without infusion reactions. So as Sanj mentioned, in conjunction with these data, we announced the active U.S. IND for our global placebo-controlled Phase II/III clinical trial as well as ongoing enrollment of the placebo-controlled investigator-initiated study in the United States, which is being conducted in parallel.

Great. Thanks for that review, John. Maybe as a follow-up here, since you mentioned the U.S. IND for your Phase II, III, based on what you've seen in the data from the Italian study, do those -- does any particular endpoint makes sense to you as you think about either hospitalization days, days to discharge or any other metrics stand out to you as a particularly clear or logical endpoint? Or are you thinking about it as more of a holistic approach?

Yes. No, that's a great question. And maybe it's a little early to speak to the specifics of our own development program, but on clinicaltrials.gov, for example, the Cleveland Clinic has listed their trial. But when you just think about the spectrum of the different studies and kind of what matters to patients and physicians, I think the critical metric is respiratory-failure free survival, the idea that these are patients who are hypoxic and are failing -- and are headed down a course towards mechanical ventilation and death. And so a therapy that can interrupt that downward spiral and allow patients to breathe on their own and breathe room air would be important. And then ultimately, of course, the longer-term outcome of preserving life, so therefore, a reduction in death.

Okay. That makes sense, I think from a mortality perspective. Maybe staying on the subject here in Mavri, one of the things we hear from KOLs when we speak with them about PCA, and giant cell arteritis treatment here. Is that there is -- definitely in terms of the treatment paradigm there has been an increasing shift towards biologic utilization. So from your perspective, based on the available data, how do you think Mavri compares to something that's on the market already like ACTEMRA, both perhaps from an efficacy perspective and from the safety seen so far.

Sure, Paul. So tocilizumab or ACTEMRA is an inhibitor of IL-6. And so of course, it's approved to treat giant cell arteritis as an adjunct to start. And that's an advancement for patients. Nevertheless, we believe that there's still a remaining significant unmet medical need. And that's because IL-6 is downstream. So only after a critical cell type, the macrophage has been activated. So IL-6, as you know, is a cytokine that's produced at the site of inflammation. It goes to the liver, and it signals the synthesis of C-reactive protein, which is a marker that we can follow in the bloodstream. So of course, by inhibiting IL 6, you reduce the production of CRP but the effect on the underlying inflammation is never -- is more limited. And so we believe that the GCA pathophysiology may actually be driven more by GM-CSF upstream. And in fact, we've been assembling data to that effect. And that means that mavrilimumab, they actually be targeting the cytokine that's responsible for the critical pathological steps of the disease. And so to speak to the data over the past year, we sponsored data presentations by external academic scientists, which both support the mechanistic rationale for targeting the GM-CSF receptor alpha in these patients with giant cell arteritis, we also have data that have demonstrated the inhibitory effect of mavrilimumab in blocking these disease pathways. So 2 key pieces of data. First, at the American College of Rheumatology meeting in November. And in fact, even at the ULR meeting this past week, Dr. Maria Cid from Barcelona, provided data that GM-CSF pathway and the key mechanisms downstream are activated at the genetic level, the RNA and protein level in the arteries of GCA patients, and that's compared to healthy controls. And she also demonstrated that mavrilimumab inhibited production of inflammatory molecules that are characteristic of GCA pathophysiology. She did that in an ex-vivo culture model of arteries from giant cell arteritis patients. And also at the ACR meeting last November, Dr. Connie Weyand from Stanford presented an in vivo model of human GCA, in which she showed that mavrilimumab reduced arterial inflammation and gamma interferon production. And of course, gamma interferon is key to giant cell formation, which is the core of this disease mechanism.

Right. That's very helpful, John. As we think about your upcoming data readout later this year, can you maybe remind us where -- what is the population you're evaluating Mavri in here in terms of GCA and also in terms of endpoints, what you look for with regard to these patients?

Sure. So the trial is a 6-month trial of 2 populations of patients in 2 cohorts, a new onset patient population as well as a relapsing refractory patient population. And that's because -- specifically in the relapsing refractory population, that tocilizumab, I think, struggled a little bit more, in terms of the clinical outcomes. And so this provides an opportunity for showing potentially differentiation.

Great. As you think about those two populations, John, or maybe if Q wants to chime in here, what seems like the better opportunity in your mind? Is it this frontline really presenting patients versus the refractory patients that you talked about? And will you focus on one more than the other, you did talk a little bit about how tocilizumab has not performed particularly well in that refractory population.

Q, you want to take that?

Well I could say -- I mean, maybe the best way to think of this is we believe there's still an attractive opportunity for Mavri in GCA, despite the Toci indication. That does remain an unmet need. And more of it's going to come down to the data, the efficacy and safety that we see with Mavri and how that stacks up. So we believe that given the fact that you have still about 50% of patients on CAPS on Toci relapse, while another 50% of those trying to come off steroids relapse, there still remains a high unmet need, giving Mavri an opportunity there.

And just to remind -- this is just a reminder, I mean, the overall prevalence perspective, this is between 7,500 and 50,000 patients, and that's in the U.S. alone. And nearly all of those patients have been treated with corticosteroids and about 50% of these can't be tapered off steroids. So hence, these patients often become steroid dependent for many years. And we've talked about there being only 1 FDA approved therapy for GCA, that's, ACTEMRA, as Q just mentioned. But we are conducting that solid double-blind, placebo-controlled randomized global Phase II trial. And that's in both new onset and refractory disease. I mentioned, I think, earlier in the year that when enrollment is complete, and we expect to have data as planned in Q4 of this year. But as far as which population we'll be focusing on, it's really newly diagnosed and refractory patients, we like the upstream mechanism of Mavri, it's upstream certainly of IL-6, being an anti GM-CSF. And we think we've designed the right study to assess the opportunity in both of those patient populations, and that's exactly what we intend to do.

Great. Sanj, and maybe as a follow-up here in terms of the GCA market. You talked a little bit about the population. Could you maybe talk a little bit on the -- about the commercial dynamics here? And as you think about going to market in the not-too-distant future here, either you Sanj or Q and thinking how does -- what kind of sort of pricing makes sense here, given that it could potentially be something that's differentiated versus ACTEMRA?

I mean maybe, Q, I'll let you comment on that, but certainly, the data will be very important. Right? And our goal, obviously, is to be very much differentiated and be a steroid-sparing option, not as an adjunctive therapy. It's obviously a little too early to talk about price as we haven't got the results yet, but it will be definitely data driven. Q, anything to add there?

No. I think, Sanj, you nailed it. The efficacy and safety profile and that risk-benefit is going to be critical. And maybe just to highlight potentially the MOA side being upstream of IL-6 and the broader impact on the GCA and the actual disease itself, the impacts on the arterial walls. And so there's so much still we're going to learn about this space. But I think there are going to be opportunities for us to position ourselves and differentiate ourselves and be data driven.

Great. Earlier in the discussion, you talked about your collaboration with Gilead and specifically, their Kite subsidiary to evaluate Mavri plus Yescarta in the refractory DLBCL population. Can you maybe talk -- what is -- a bit about the scientific rationale here? What is the need that Mavri serves here in the Car T paradigm? And how do you view this opportunity as a potential another leg of growth for Mavri?

Yes, maybe I'll cover just the second half of your question, and I'll flip to the first half. But certainly, I think, as I mentioned earlier, we really view the efforts in Mavri across COVID-19 pneumonia and hyperinflammation as well as the GCA program and the collaboration with Kite in CAR T and CRS, indicative of the broader potential of the mechanism across the whole host of immune-mediated diseases. And to answer your question on the scientific rationale, I think treatment-related induction at GM-CSF through CAR T cell therapy have been identified through clinical, translational and preclinical studies, really as a potential key signal associated with the side effects of CAR T, including CRS, cytokine release syndrome, as well as neurological toxicities. So I think we're seeing preclinical evidence showing the potential for interruption of GM-CSF signaling to disrupt the CAR T cell-mediated inflammation importantly, without disrupting the antitumor efficacy. So I think as a whole, we really do like the approach and the mechanism approach that we've taken. But John or Q, anything to add there as far as the overall program?

Sure, Sanj, perhaps just real quickly, going into the literature. [indiscernible] was in blood of 2019 actually speaks to your points about the role of GM-CSF in the on-target cytokine storm phenomenon. So in this analogue xenograft model in cytokine release syndrome and neuroinflammation, GM-CSF neutralization actually resulted in a reduction in myeloid and T-cell infiltrates in the CNS as well as a significant reduction in the neuro inflammation and prevention of CRS. And in fact, the GM-CSF deficient CAR-T 19 cells maintained their normal functions and actually had enhanced antitumor activity in vivo. And so thus, there is improved survival overall compared to the CAR-T therapy alone with the analogue xenograft model. So very encouraging data from the literature.

Great. And can you maybe just remind us -- this is focused on the refractory large B-cell lymphoma population, but obviously, Mavri could potentially make sense with other CAR-T paradigms. So I was just wondering, can you maybe remind us how you think about the opportunity set here? What is the rate of CRS, broadly speaking, that we've seen across these early-stage CAR-T trials and especially as it's been commercialized in the real-world setting.

Sure, Paul. This is Eben. So early on in the days, there were around 40 or so percent rate of neurotoxicity. That has come down as physicians have had more experience with the treatment algorithm in the current therapies, and I think it's hovering around 20% to 30% now.

Okay. That's very helpful. We're coming up on time. So I don't want to ignore the rest of the pipeline. And so maybe we can talk a little bit about what your development efforts recently in PN have been. And so can you maybe talk a little bit about how you think Vixarelimab will fit into the PN treatment landscape, particularly given the Phase II and how you think your data stacks up versus some of the competing data that was also recently announced?

Yes. Absolutely. This is Eben. I'll take that one again. So it's, first, important to note that there are no FDA-approved therapies and limited therapeutic options demonstrating efficacy in PN. In terms of that treatment algorithm, first-line is usually topicals including steroids, calcineurin inhibitors. Second line moves to the oral systemic therapy, corticosteroids, that sort of thing and maybe some UV phototherapy. Third line involves harder core systemic immunosuppressant such as methotrexate, cyclosporine and even thalidomide. And so it's potentially great for patients that there are systemic therapy options available in-development that are in randomized placebo-controlled trials. Now both Vixa and nemolizumab, both inhibit IL-31, and that's clearly been shown to inhibit pruritus. But Vixa really also inhibits oncostatin M, which we believe may drive both fibrosis and hyperkeratosis, which may translate into lesion improvement over time. And that's exactly what the Phase II program [Technical Difficulty] stating significant results in both pruritus and nodule early impairment [Technical Difficulty]

Eben, you're breaking up here a little bit. I think we lost you.

I can take over from there. I mean, so basically, we're saying, obviously, we're looking forward to the differentiation from oncostatin M. But certainly, the Phase IIa data we saw in prurigo nodularis showed us we met the primary endpoint. We also saw some very nice nodule response. So I think differentiation is going to be the key there. And so we are moving as fast as possible into the dose-ranging study, and we're very excited about that first-in-class mechanism.

Great. We have about a minute or 2 left here. And maybe just to end our discussion. Could you maybe think about how you're leveraging -- when you think about leveraging other areas where chronic pruritus is sort of a characteristic of the disease? And when can we expect updates from that particular Phase II study, particularly in the chronic population? With pruritus.

Eben, are you on or should I take that? I think Eben's not on. Okay. So basically, yes, we had data recently, actually from a Phase II study, a basket study with chronic pruritus, and we had several cohorts in the plaque psoriasis, chronic idiopathic pruritis, lichen simplex and idiopathic urticaria and lichen planus. 4 out 5 of those cohorts showed very encouraging data, as you say, Paul, on the pruritus side. So we're following that, some -- we're not saying that our next indication will be any one of those per se. I think prurigo nodularis at this point is our first indication, but that data that we've seen and certainly 4 of those 5 have shown that there is a broad utility for this program, and there is a strong prolific angle. But obviously, the OSM is going to be very important as far as nodule responds. So we'll keep following the data. We've got some additional respond analysis to do and biomarker analysis to do. Across those indications that will help us finalize next steps. We'll initiate the Phase IIb dose rating study and then really look to potentially broaden that program, as you say, in those prolific angles.

Great. Thanks for that, Sanj. Unfortunately, we've come up here on our time limit, so we'll have to end the discussion there. My thanks to the management team from Kiniksa for participating here in the Goldman Sachs Conference. And we'll end the session on that note. Thank you very much, team.

Thanks, Paul. Thank you very much. Bye.

Thank you. Bye.