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

Okay. We'll go ahead and get started. So welcome to the afternoon session of the 2020 JPMorgan Health Care Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Matt Bannon and Tess Romero from the team. Our next presenting company is Kiniksa. And presenting on behalf of the company, we have CEO, Sanj Patel. Sanj?

Thanks, Anupam. Good afternoon. It's great to be here. This is actually the 10th time I have had the opportunity of presenting at this conference. And as usual, I want to thank JPMorgan and Anupam, for hosting us today. We have a lot to go through. So let's get started. I'm going to start with an overview of our corporate strategy, review our pipeline and also the multiple clinical data readouts that we have coming up this year. First, please note that I will be making forward-looking statements today that are subject to risks and uncertainties. A review of those statements and risk factors are found on this slide as well as under the heading of Risk Factors in our SEC filings. Kiniksa is focused on autoimmune and autoinflammatory diseases. Our product candidates are based on validated mechanisms or strong biologic rationale, and they target underserved diseases and offer the potential for differentiation. This is our pipeline with the stage and first indication for our multiple clinical stage assets. And starting with recurrent pericarditis, this is an auto inflammatory cardiovascular disease and rilonacept is in a global pivotal Phase III study, called RHAPSODY. Giant cell arteritis, or GCA, is a chronic inflammatory arterial disease and mavrilimumab, or mavri, for short, is in a global Phase II study. Prurigo nodularis is a chronic inflammatory skin disease, and KPL-716 is in a Phase II study. And we're also in a Phase II study with 716 in multiple diseases characterized by chronic pruritus. And we started a Phase I study with our KPL-404 CD40 program. And that started in 2019, which was ahead of schedule. I mentioned that our clinical stage assets are based on validated mechanisms or strong biologic rationale. And to walk you through those mechanisms, IL-1 alpha and IL-1 beta are cytokines that have shown to play a key role in auto inflammatory diseases. And rilonacept blocks the signaling of both IL-1 alpha and IL-1 beta. GM-CSF is a key growth factor that's involved in auto inflammation and autoimmunity, and mavrilimumab blocks the signaling of GM-CSFR. And IL-31 and oncostatin M are key cytokines that have been implicated in prurigo nodularis. And KPL-716 was designed to target both of those cytokines. And the CD40 and CD40L interaction, we believe, is a rather attractive mechanism for targeting T-cell mediated B-cell-driven autoimmune diseases. Our clinical-stage assets target underserved diseases, and as I said, offer the potential for differentiation. The estimated U.S. prevalence for recurrent pericarditis is 40,000 patients which are seeking medical treatment for that condition. And upon approval, rilonacept would potentially be the first FDA-approved therapy for that debilitating disease. The estimated U.S. prevalence for giant cell arteritis is between 75,000 and 150,000 patients. There is only one FDA-approved therapy, and we believe mavri works more upstream than that molecule. The estimated U.S. prevalence for prurigo nodularis is approximately 300,000 patients, and there are no FDA-approved therapies. And KPL-716 is a first-in-class mechanism. And the external proof-of-concept for the CD40, CD40L pathway has been established in a broad range of autoimmune diseases. And the KPL-404 profile suggests that we could have a best-in-class molecule here, which is obviously very exciting. We have multiple clinical data readouts coming up this year, and they start with top line Phase II data in prurigo nodularis from KPL-716 in the first half of this year. We've also got interim Phase II data in multiple diseases characterized by chronic pruritus, also from 716 and also in the first half of this year. We have the pivotal topline Phase III data in recurrent pericarditis from rilonacept and that's in the second half of the year. And we have top line Phase II data in giant cell arteritis for Mavri, also in the second half of the year. And we have topline Phase I data from our KPL-404 CD40 program. So I'll now walk you through each of these programs in a wee bit more detail. So as you can see, we're progressing rilonacept in our first indication, which is recurrent pericarditis. But it's important to note that it's an already approved biologic for CAPS which is an ultra-rare autoinflammatory disease. And just last year, late last year, the FDA granted breakthrough therapy designation for the treatment of rilonacept in recurrent pericarditis. And we believe that's an important step forward for patients because it underscores the severity of the disease and the potential of treatment with rilonacept. So what is the definition of recurrent pericarditis? All patients are deemed recurrent if they have an episode after a symptom-free period of 4 to 6 weeks. Current standard clinical practice is treatment with NSAIDs with or without colchicine. And while that might be sufficient for some patients, approximately 20% to 30% of the patients experience a painful recurrence. And in these cases, corticosteroids are used. As a third-line treatment, some physicians also have to use other systemic agents because many patients can't be weaned off steroids or have multiple recurrences. And some patients even have a pericardiectomy, which is the removal of the sack around the heart and obviously, an incredibly invasive procedure. Recurrent pericarditis episodes are painful, debilitating and highly disruptive to the quality of life of patients. And the key areas of unmet need that patients are seeking to address are the resolution of their episodes, the prevention of future episodes, steroid-sparing disease control and improvement in their quality of life. In fact, physicians and patients often have to resort to opioids to manage their pain. And it's the sheer unpredictability and the severity of the disease that could often lead to significant anxiety and depression in patients. The clinical development plan for rilonacept was designed to generate data on clinically meaningful outcomes and our successful and completed Phase II study provided the first evidence that rilonacept could improve clinical outcomes in the Phase II study. Importantly, the safety profile was consistent with the FDA-approved label for CAPS. I am happy to reiterate a press release we put out just this morning that announced that we've met our target enrollment for our Phase III pivotal study, RHAPSODY. We'll continue to enroll patients for a limited period to facilitate the number of primary efficacy endpoint events. And based on enrollment, we're on track to have the topline pivotal data in the second half of this year. The full and final rilonacept Phase II data were presented at AHA just last November, and they were very well received. What you see here is a marked resolution of pericarditis episodes in symptomatic patients. You also see a rapid and sustained improvement in both the reported pain and inflammation -- importantly, after only one dose. And there was a persistent and clinically meaningful response throughout the 6-month study. These data show the potential to discontinue corticosteroids without a pericarditis recurrence. In the middle, you see there was a decrease in the annualized incidence of pericarditis episodes while patients were on treatment. And on the far right, you see that we had an improvement in the quality of life scores. We are becoming increasingly excited with the potential commercial opportunity with rilonacept. And that's based on our ongoing market research and our preparations for commercialization. Of the 40,000 patients that are seeking medical treatment for recurrent pericarditis, we believe, around 14,000 of these are most addressable with rilonacept. Patients fall into 3 main subgroups: Refractory patients, steroid-dependent patients and those patients that have multiple relapses. We plan to focus on all of those patients first because they have multiple unmet needs and physicians have actually indicated an interest to treat across all of those subgroups. We've developed the commercial strategy. We'll plan to have a specialty cardiology sales force of approximately 30 reps that are calling on the high-volume specialists and they will be supported by our current MSL, Medical Science Liaison team as well as an efficient digital marketing effort. Based on our ongoing market research, we believe that patients will be treated for at least 6 to 12 months, and that's consistent with the data set that we will provide to the regulators as part of our sBLA strategy and filing. But on top of that, some physicians have actually expressed an interest to treat beyond the initial 6 to 12 months. And in terms of pricing, we expect this to be in line with the high unmet need in rare diseases. And the price for rilonacept or ARCALYST in CAPS is $20,000 a month, based on the weekly administration. Our first indication with mavrilimumab is giant cell arteritis. And this is a chronic inflammatory disease of the medium to large arteries and can often result in permanent blindness. In fact, patients are often on steroids for several years. I mentioned there is only one FDA-approved therapy for giant cell arteritis, and that's as an adjunct to steroid therapies. And we believe, does not address the underlying cause of the disease. Mavri, however, is a GM-CSF receptor inhibitor, and there is a potential for differentiation because it acts more upstream. And importantly, GM-CSF is a key growth factor in giant cell arteritis and targets the upstream cytokine responsible for the disease. In 2019, we presented preclinical data that supported the mechanistic rationale for targeting GM-CSF in giant cell arteritis. At the EULAR Conference, in June, we showed data that showed that GM-CSF and its receptor were elevated in GCA biopsies compared to a control. And at ACR, in November, we presented data whereby mavrilimumab reduced arterial inflammation in an in vivo model, again, compared to a control. I'm happy to report our -- and reiterate our press release from this morning announcing that we've achieved the target enrollment for our global Phase II study in giant cell arteritis. We'll continue to enroll patients for a limited period to help facilitate [ the ] number of primary efficacy endpoint events. And again, based on enrollment, we remain on track to have topline data in the second half of this year as planned. I also want to reiterate a press release that we put out late last year, which announced the collaboration between Kiniksa and Kite Gilead. And this is the study of mavrilimumab with Yescarta in patients with relapsed or refractory large B-cell lymphoma. And to see whether mavrilimumab could help with some of the CAR T-cell-mediated inflammation. Our first indication for our third clinical program, KPL-716, is prurigo nodularis. This is a chronic inflammatory skin disease with pruritic lesions. KPL-716 is a monoclonal antibody inhibitor that targets OSMR beta, and blocking IL-31 has shown to have a marked reduction in pruritus. But there's also the potential for differentiation and disease modification by blocking OSM, which drives fibrosis, inflammation and hyperkeratosis. The preclinical, clinical and recent external data with IL-31 support the further development of KPL-716. And what you see here is data from our single dose and repeated single dose Phase Ib study. We saw a rapid and sustained antipruritic effect. And this was in patients with moderate to severe atopic dermatitis, which was used as a proxy for prurigo nodularis. We're enrolling in the Phase II study in prurigo nodularis. The primary efficacy endpoint here is weekly average worst itch NRS at 8 weeks. We're on track to have data in the first half of the year. And we're also enrolling in a Phase II study in multiple diseases characterized by chronic pruritus. And again, we're on track for that interim data from select cohorts in the first half of the year. Our fourth program, KPL-404, is already generating significant interest. The external proof-of-concept has been established in a broad range of autoimmune diseases, including Sjogren's disease, lupus, rheumatoid arthritis, solid organ transplant and Grave's disease. It's a monoclonal antibody inhibitor of the CD40, CD40L interaction, which we believe is an attractive mechanism for blocking T-cell mediated B-cell driven autoimmune diseases. We're enrolling and dosing subjects as part of a Phase I study where we're assessing receptor occupancy and TDAR, T-cell dependent antigen response. And that should give us a good level of understanding of the amount of target engagement for this molecule. A recap of the multiple clinical data readouts that we have coming up this year. We've got topline Phase II data in prurigo nodularis, interim Phase II data in select cohorts in multiple diseases characterized by chronic pruritus, pivotal topline Phase III data in recurrent pericarditis, topline Phase II data in giant cell arteritis, and topline Phase I data from our CD40 program. In summary, Kiniksa is focused on rare diseases with unmet need and we have a number of potentially attractive commercial opportunities in front of us. Our year-end cash balance in 2019 was $233 million and that funds us into the second half of 2021. And importantly, allows us to achieve multiple clinical data readouts. And in fact, funds us well beyond those. And as you've seen, we've got a full clinical pipeline and we are incredibly enthusiastic about the future. We're in the Sussex room for the breakout session, and we'll be happy to take any questions you have there. Thank you.