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Incyte Corporation (INCY)

Q3 2018 Earnings Call· Tue, Oct 30, 2018

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Transcript

Operator

Operator

Greetings and welcome to the Incyte's Third Quarter 2018 Earnings Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mike Booth, Vice President of Investor Relations for Incyte. Mike, please go ahead.

Michael Charles A. Booth - Incyte Corp.

Operator

Thank you, Kevin. Good morning and welcome to Incyte's third quarter and nine-months 2018 earnings conference call and webcast. The slides used today are available for download on the Investors section of incyte.com. I'm joined on the call today by Hervé, Barry, Steven and Dave, who will deliver our prepared remarks, and by Reid, who will join us for the Q&A session. Before we begin, we'd like to remind you that some of the statements made during the call today are forward-looking statements, including statements regarding our expectations for 2018 guidance, the commercialization of our products and our development plans for the compounds in our pipeline, as well as the development plans of our collaboration partners. These forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our 10-Q for the quarter ended June 30, 2018 and from time-to-time in our other SEC documents. We'll now begin the call with Hervé. Hervé Hoppenot - Incyte Corp.: Thank you, Mike, and good morning, everyone. I am pleased to report that Incyte continues to perform very well across all aspects of the business. We have recently delivered exciting data at both the EADV Congress and at ESMO, and we are looking forward to seeing many of you at ASH in San Diego. Total product revenue continues to grow nicely, and we recognized a 25% increase in nine months revenue versus the same period last year. Revenues of over $1.2 billion in the first nine months of 2018 included over $1 billion in Jakafi sales and over $160 million in royalties from Jakavi and Olumiant, reflecting strong demand for both ruxolitinib and baricitinib on a global basis. It's important to note that Q3 net sales for Jakafi were negatively…

Barry P. Flannelly - Incyte Corp.

Analyst

Thank you, Hervé, and good morning, everyone. Patient demand for Jakafi remains very strong, and we are seeing good uptick in both MF and PV indications. Slide eight shows a robust growth in patient demand for both MF and PV. As you can see, the total number of MF patients currently on Jakafi, shown in blue, continues to rise, and the pool of MF patients on therapy continues to be greater than PV, shown in orange. The total number of PV patients on Jakafi is growing faster than MF, and we continue to expect that in time the number of PV patients taking Jakafi will overtake MF. The sales bridge, provided on the left-hand side of slide nine shows continued demand growth in Q3 and the effect of inventory changes on net sales. We saw an unexpected destocking at several large customers late in the third quarter, leading to a negative inventory effect of approximately $8 million in the quarter. The nine-month sales data shown on the right-hand side of slide nine where effects of changes in inventory are normalized shows a strong 21% growth over the same period last year. The number of new patient starts is typically a leading indicator for sales performance, and Q3 new patient demand data are encouraging and provide us with good momentum as we enter the fourth quarter. Giving our confidence in the full-year outlook today, we have adjusted Jakafi guidance by lifting the lower end of the prior guidance range. Slide 10 shows the consistent yearly growth of Jakafi, adding more than $200 million in net product revenue each year since 2014. We are on target to continue that trend again for the full year of 2018, given that the midpoint of the new guidance range represents more than $250 million in increased Jakafi revenue versus the full year of 2017. I am very pleased that both indications are driving growth as we continue to secure new patients, while also maintaining current patients on therapy for longer. Given the success of the REACH1 trial, we continue our readiness efforts for potential approval of Jakafi in steroid refractory acute GVHD. Our team has made excellent progress in educating physicians about the benefits that Jakafi provides in both MF and PV indications. And I have every confidence the team will do an equally outstanding job for patients with GVHD. We submitted the sNDA on schedule during the third quarter based on positive results from REACH1 in patients with steroid refractory acute GVHD, and the FDA has recently accepted it for Priority Review. As we detailed last quarter, we believe our team's size and structure has already been optimized, and we are ready to launch immediately in this indication, if approved. With that, I'll pass the call over to Steven for an update on our portfolio.

Steven H. Stein - Incyte Corp.

Analyst

Thanks, Barry, and good morning, everyone. We believe that JAK inhibition has significant potential as a treatment for graft versus host disease, and we have two pivotal programs that span several aspects for this devastating and often fatal disease. As Barry touched on, we were pleased to have the ruxolitinib sNDA accepted by the FDA for Priority Review based on the results of REACH1. Beyond REACH1, we have three ongoing Phase 3 trials that are all currently expected to yield results next year. REACH2 and REACH3 are evaluating the use of ruxolitinib in steroid refractory acute graft versus host disease and steroid refractory chronic graft versus host disease, respectively. GRAVITAS-301 is the first pivotal trial that is evaluating our JAK1 selective inhibitor, itacitinib, in patients with treatment-naïve acute graft versus host disease. Early next year, we expect to launch a second Phase 3 trial of itacitinib, this time in patients with steroid – with treatment-naïve chronic graft versus host disease. There are a significant number of new patients each year that would become eligible for treatment with either itacitinib as a first-line treatment or ruxolitinib, following treatment with steroids, if our trials are successful and we obtain regulatory approvals. On slide 14, we have included data for pemigatinib, our FGFR1/2/3 inhibitor, which was presented recently at ESMO in Munich. If you recall, we presented some initial data from this group of patients at our R&D day in June this year, which showed a disease control rate of 82%, an overall response rate of 24%, and a 6.8-month median progression-free survival. You can see here that as patients remained on therapy, responses have been more durable, and more patients have become responders such that the response rate is now 40% with the median progression-free survival of greater than nine months. Importantly,…

David W. Gryska - Incyte Corp.

Analyst

Thanks, Steven, and good morning, everyone. The financial update this morning will include GAAP and non-GAAP numbers. For a full reconciliation of GAAP to non-GAAP, please refer to our press release. For the third quarter, we recorded $450 million of total revenue on a GAAP basis. This is comprised of $348 million in Jakafi net product revenue, $20 million in Iclusig net product revenue, $51 million of Jakavi royalties from Novartis, $11 million in Olumiant royalties from Lilly, and $20 million of contract revenues for a milestone earned from Lilly for the commencement of the Phase 3 program in lupus. Total revenues for the quarter on a non-GAAP basis were $430 million and exclude the $20 million milestone from Lilly. Our Jakafi gross to net for the quarter was 13.5%, and we expect that our gross net adjustment for full-year 2018 will be approximately 14%. Our cost of product revenue for the quarter was $19 million on a non-GAAP basis. This includes the cost of goods sold for Jakafi and Iclusig, and then payments of royalties to Novartis on Jakafi net sales. Our R&D expense for the quarter was $251 million on a non-GAAP basis, primarily driven by clinical development programs, and our SG&A expense for the quarter was $85 million on a non-GAAP basis. Moving on to non-operating items, we recorded GAAP and non-GAAP net interest income of $10 million in the third quarter. Our net income for the third quarter on a non-GAAP basis was $83 million, which is double that reported for the same period last year. Looking at our year-to-date results, our net income on a non-GAAP basis was $137 million. We ended the third quarter with $1.4 billion in cash and marketable securities, and we expect to end the year with approximately the same amount.…

Operator

Operator

Thanks. Our first question today is coming from Salveen Richter from Goldman Sachs. Your line is now live. Salveen Richter - Goldman Sachs & Co. LLC: Good morning. Thank you for taking my questions. So, I have two questions on graft versus host disease. So firstly, in light of the upcoming PDUFA date for the REACH1 study, could you comment on the education required here on the sales side and any additional build you might require in terms of your sales force? And then, secondly, in light of this positive data, how does that read through to the other RUX studies in graft versus host as well as itacitinib? And then, specifically, for itacitinib, what is the benefit of JAK1 alone in the treatment-naïve setting versus JAK1/2? Thank you.

Barry P. Flannelly - Incyte Corp.

Analyst

Hi, Salveen. This is Barry. I'll take the first part of your question and hand it over to Steven for the second part of the question. So, in terms of the build, so we already have, at the – throughout this year, we've added 25 sales representatives, three MSLs, and two oncology nurse educators. And that was to get ready, in fact, for GVHD but also to take advantage of continued growth opportunities for Jakafi in myelofibrosis and polycythemia vera. So, those oncology sales representatives are actually positioned around the top centers that do stem cell transplants and where most GVHD would be found. So, I think, as we said before, the top 50% – at the top 50, stem cell transplant centers account for about 70% of the transplants. So, we think it's really targeted. Our training is beginning now for – so our training materials are all prepared in terms of educating our internal teams, including the sales teams. We call on many of these targets already, these – about 50% of the physicians that are doing transplants because, remember, some of them are doing transplants for myelofibrosis patients. So, we know the centers. We've been profiling the centers. We have another team that we call our national account managers that have been making sure that we'll be able to have Jakafi on formulary for steroid-refractory acute GVHD. So, we think we're well-prepared in terms of that education. And then, of course, we'll educate healthcare professionals about the benefits that Jakafi provides in this patient population. And we're fully prepared in putting together materials for that. With that, I'll hand it over to Steven.

Steven H. Stein - Incyte Corp.

Analyst

Thanks, Barry. Thanks for the question, Salveen. So, you asked about the read-through from the REACH1 results to the REACH2 program, which is in steroid-refractory acutes as well, but a randomized study against best available therapy, and then REACH3, which is in chronic graft versus host disease and also randomized study. Overall, the read is positive, given that it's JAK inhibition with a few nuances. Acute disease is generally an apoptotic disease, whereas chronic disease is more a fibrotic disease. But given that we have proof of concept in both entities, we obviously feel strongly about the likelihood of probably of success here and thus we conducted these large Phase 3 programs. So, overall positive reads there. The same applies to itacitinib, even though it's more selective for JAK1. Again, JAK inhibition being important across the spectrum of graft versus host disease, let me just remind you of itacitinib's proof of concept data at actually a few years ago, which showed a very high response rate in steroid-naïve as well as in steroid-refractory. But the steroid-naïve response rate was 20 points higher and thus gave us proof of concept to go ahead with GRAVITAS-301. Why is it important? Because of the sparing of JAK2, there's expected to be relatively less cytopenias. And given that these patients are steroid-naïve acute to immediately post-transplant, what they're struggling with in terms of morbidities, often cytopenias in terms of low platelets, low white cells, anemias. So, the cytopenias-sparing effect should be helpful and should translate to increased success and tolerability. Thanks. Salveen Richter - Goldman Sachs & Co. LLC: Thank you.

Operator

Operator

Thank you. Our next question is coming from Marc Frahm from Cowen and Company. Your line is now live. Marc Frahm - Cowen & Co. LLC: Thanks. Just one – kind of following up Salveen, when we think about the itacitinib data and GRAVITAS-301, can you talk about what type of effect do you think you need to show to kind of justify moving an expensive therapy kind of into that front line in more of a contract-type of setting, like transplants? And is it just the response rate? Or is there some other aspect that we should really be focusing on to justify that?

Steven H. Stein - Incyte Corp.

Analyst

Yeah, thanks for the question. Again, it's Steven. Generally speaking, steroids have approximately a 40% to 50% response rate with the attendant side effects, particularly when they're used over the long-term, which are well-known in terms of steroid side effects. So, from our point of view, a response rate that's one north of that and in absolute numbers can be quantified, but it should be higher than steroids. And then, in terms of what we know, in terms of tolerability, and you have got ample evidence of long-term use of ruxolitinib in MF and PV now. The profile is very different from long-term use of steroids. So, the effect would have to be that higher response rate and a better tolerability profile that would enable people to get off of the steroids, and that's what we're looking for in GRAVITAS-301. And that would be an additional clinical benefit to the actual treatment of graft versus host disease is the ability for patients to be weaned off of the steroids. Marc Frahm - Cowen & Co. LLC: Okay, great. And then, just for Barry, on the thing about pemigatinib, and you're potentially launching or getting filed next year in cholangiocarcinoma, could you just talk about the build-up that is going to need to be done, the timing of that for commercial organization and solid tumors that doesn't really exist right now?

Barry P. Flannelly - Incyte Corp.

Analyst

Well, we're hopeful that will get approved as soon as possible. But we're just working on exactly the size of the team that we'll need for this patient population in cholangiocarcinoma with FGFR2 translocations. So, those efforts are really ongoing, and we'll continue to update you as we get closer to an actual launch date. Marc Frahm - Cowen & Co. LLC: Okay. Thank you.

Operator

Operator

Thank you. Our next question is coming from Cory Kasimov from JPMorgan. Your line is now live.

Unknown Speaker

Analyst

Hey, guys, this is Sean (27:09) on for Cory. Congrats on the quarter. And just a couple questions on cholangiocarcinoma. So, the updated results from ESMO look to be quite promising. It actually looks like there was a significant portion of patients in whom the response took a bit longer to evolve. In your previous update, I think there was like 11 out of 45 responses versus 19 out of 47 responses at ESMO. So, just kind of wondering the kinetics of the response surprise you a bit? And as a follow-up, maybe you could share with us some color around your filing plans. Is there a chance that we could potentially see a BTB (27:43) Priority Review in this indication? And are there discussions currently ongoing with the FDA?

Steven H. Stein - Incyte Corp.

Analyst

Yeah, Sean (27:49), it's Steven. Thank you for your question. Yes, it's a good surprise, right? The ESMO updated data showed that centrally reviewed response rate of 40%, which is robust, and as you noted, increased with time. For reasons in one particular tumor versus others is we see that it's not entirely clear. But obviously the biology of that particular FGFR2 translocated cholangio is such that over time you can get increased cytoreduction. Probably, a clue for that came if you look at the entire waterfall plot is the disease control rate is north of 80%. So, just about everybody is having some degree of cytoreduction from the get-go. And obviously, over time, those improved in a substantive way that were also really durable. So, given the context, given that this is second-line cholangiocarcinoma, given that chemotherapy in the setting has maybe a 10 – at a stretch 15% response rate with very short progression pre-survival, we believe these results are now in the territory to meet potential regulatory approval-type data. And to – further to your question, we will be discussing, of course, with the regulatory authorities, does this meet breakthrough designation criteria, and as such, will it qualify for Priority Review? And again, we feel strongly that that's starting to look increasingly to be the case. I am focused in my comments on the FDA. We didn't mention Europe because the root there for single-arm studies is harder. But given this updated data set, we will obviously be discussing these in Europe with the regulatory authorities as well. So this now meet potential regulatory approval criteria. So, very encouraged by the data set and surprised in a good way by the increase in response rate that's durable over time.

Operator

Operator

Thank you. Our next question is coming from Geoff Meacham from Barclays. Your line is now live.

Geoff Meacham - Barclays Capital, Inc.

Analyst

Morning, guys, and thanks for the question. Dave, I also want to offer up some congrats on your retirement. Seems like we've had this conversation before. Barry, another one on Jakafi, when you look at the GVHD opportunity, what do you think could be the initial uptake curve based on REACH1 and the unmet need. I guess my sense is do you think docs will want to wait ultimately until REACH2 or – 2 or 3 data are fully out? And then I have one follow-up for Hervé.

David W. Gryska - Incyte Corp.

Analyst

No, Geoff, I actually think the uptake will be quite good, obviously, what the patient population is. Steroid-refractory GVHD in the United States, we say it's around 1,500 patients. We think that the data we've shown so far are compelling, better than anything else in this particular setting, able to get patients off of steroids. Obviously, these patients are very, very sick and they really need to get their GVHD under control right away. And it looks like we're able to achieve that with the profile that we have. So, I'm very encouraged about that opportunity. And then we're looking forward to getting approval for chronic GVHD and we think that'll be a good opportunity as well. So, we're looking forward to both of these indications.

Geoff Meacham - Barclays Capital, Inc.

Analyst

Okay. And then, Hervé, you've got a great franchise in Jakafi which obviously could drive pretty robust profitability. And I argue you're getting zero credit for pretty much anything in the pipeline beyond what's in Phase 3. So, why continue to develop so many assets that are earlier stage? Do you think you would add more value by, for example, narrowing the pipeline breadth and focusing a little bit more on profits today? Thanks. Hervé Hoppenot - Incyte Corp.: I think your question is really about our overall R&D investments or what we believe is that the quality of the science we have here at Incyte, the quality of the discovery team is now proven. We spoke about ruxolitinib and baricitinib already approved, commercially available. We are speaking of now pemigatinib, itacitinib, capmatinib, so that will be like five molecules that are coming from our own discovery group that have been now very close to crossing the line and showing a lot of very promising data. So, it shows that R&D done the right way can be extremely productive. And before you have late-stage products, obviously you have to have early-stage products. And that's why we have a portfolio of early-stage program. We don't know yet from that portfolio which one will be the breakthrough that are moving very quickly, and which one may end up being more on hold. I must say, in terms of investment, most of it is coming from the late-stage portfolio. So, if you look at the way the investment is calibrated between early-stage and late-stage, what you see is that the pre-proof of concept program usually have a relatively modest impact on the models – I mean it's a relatively smaller impact on the R&D budget. And our choice to develop these products is really based on the data and the science and the medical need and trying to improve treatment of cancer. Or outside of cancer, as you can see, there are now a number of fairly interesting programs we have. And I must say, the atopic derm and the vitiligo program for ruxolitinib cream are, assuming we get good data from the Phase 3, are going to be very productive for our corporation. So, that being said, obviously, we are very cautious about our investments in R&D. And as I said in my remarks, the way we see the entire corporation evolve is increase profitability. I think Dave spoke about the profitability we have seen in this quarter, which was double what we had a year ago, and that's a trend over a period of time that you will see confirmed with the progress of our business.

Geoff Meacham - Barclays Capital, Inc.

Analyst

Okay. Thanks.

Operator

Operator

Thank you. Our next question is coming from Matthew Harrison from Morgan Stanley. Please proceed with your question. Matthew K. Harrison - Morgan Stanley & Co. LLC: Great. Thanks for taking the questions. I guess, one, can you just comment briefly on the inventory drawdown and whether you expect that to reverse in coming quarters or if there was a specific driver of that drawdown this quarter? And then maybe secondly, can you just comment on the – what are the key issues that you're speaking with the FDA about the Phase 3 for atopic dermatitis with ruxolitinib cream? Thanks.

Barry P. Flannelly - Incyte Corp.

Analyst

Okay, Matt, so I'll take the first part. No, we think this is one-time. Well, inventory changes periodically. We've seen it over a quarter, sometimes the inventory is above the normal range that we experience, sometimes it's below the normal range, which is what we say is two and a half to three weeks of inventory in the channel. And even if you move a couple of days one way or the other, now that's about $12 million. Was it a driver of the inventory burn off this quarter? Well, we took a 3% price increase at the beginning of September, and historically, we've seen after we take a price increase that inventory does go down, but generally it's gradually over time. This was very quick and a little bit more dramatic that we saw some destocking. To be honest, even in October that's already reversed itself. We're on budget for October, we're on budget to hit the guidance that we just gave before. We're planning to deliver close to $250 million in 2018 above and beyond what we sold in 2017. So, we're very confident moving forward. And I'll hand it over to Steven for the second part.

Steven H. Stein - Incyte Corp.

Analyst

Hi, Matt. Thanks for your question. This is Steven. I mean, they're the obvious issues, but I'll go through them. The type of things we are discussing, given the proof-of-concept work we've conducted and presented already are the dosing, the need to study more than one dose or not. The number of studies that are needed in this setting in dermatology, conventionally it's at least two studies. The size of those studies, given that the safety databases in dermatology indications tend to be 1,000 patients or north of that. And whether or not an active comparator is needed or not in these studies. I think those are the four main issues. The good news is we're very close to closure on those and we aim, as Hervé said in the call, at a minimum to get these studies going in the first quarter of 2019, if not sooner. So, we're in a good place, we have the right set of proof-of-concept data, we have agreement on most of these issues, and we should be going soon. Matthew K. Harrison - Morgan Stanley & Co. LLC: Great. Thanks very much.

Operator

Operator

Thank you. Our next question is coming from Brian Abrahams from RBC. Your line is now live.

Brian Abrahams - RBC Capital Markets LLC

Analyst

Hi. Thanks very much for taking my questions. Two questions on Jakafi lifecycle. I guess first off, I was wondering if you could talk a little bit more about the ongoing Jakafi combo studies, perhaps put a finer point on the timing for upcoming readouts and maybe give us a sense for your view what's the (37:37) overall bar there, what you would need to show from a symptomatic improvement standpoint, from intolerability to warrant potential exploration here, not just in refractory patients, but in front-line as a potential Jakafi replacement. What would be acceptable in terms of additional AEs? And then I had a follow-up.

Steven H. Stein - Incyte Corp.

Analyst

So, Brian, it's Steven. Thanks for your question. Obviously, the lifecycle management of RUX itself is incredibly important to us, given that we have patent runway in the United States and beyond at least through 2027. So, it's a large program with numerous efforts. You focused your question on one of them, which is combination work. We have various combinations ongoing. The one that you'll see that's currently the most encouraging to us, and you'll see data readouts on relatively soon in upcoming meeting at the end of the year, which we already showed you a sneak preview in 10 patients at the R&D day there's a ruxolitinib plus PI3 kinase program, the delta program with 50465. And in that early read, we showed you in the 10 patients at the R&D day, you saw both a further decrease in spleen volume in terms of actual – and a reasonably objective measure of activity as well as symptom improvement. Remember, RUX itself is such a fantastically successful drug that it's not easy to recruit these trials quickly. And most people stay on RUX for a very long time and do really well. So, the additional needs beyond, in terms of regulatory endpoints, aren't very clearly defined. We've been working with the FDA in the space because we have numerous combinations ongoing and trying to come to a very strict definition of what constitutes, if you will, "ruxolitinib failure or RUX refractoriness". And then put people appropriately on those studies to make sure we always have apple-to-apple comparisons across our programs and others. So, they're not strictly defined yet, but we've been working very carefully to get those to you. We also have ongoing programs, just to mention, with ruxolitinib plus our PIM inhibitor, which has really good pre-clinical data. And then a combination with JAK1 with itacitinib itself that's ongoing as well in patients who either can't tolerate doses of RUX or have to come off of it, and then we have a switch strategy as well. So, it's a very large combination program across all of them with the lead clinical evidence now for which you'll see updated data at the meeting end of this year is the RUX plus PI3 kinase-delta program. And hopefully, the endpoints will be more clearly defined over time.

Brian Abrahams - RBC Capital Markets LLC

Analyst

That's really helpful. And then, just to follow up to that, in terms of next generation ruxolitinib formulations, I know you recently published data on an earlier formulation. Just wondering where you are with respect to optimization. How much cytopenia reductions and/or improvement in efficacy you could potentially achieve and might need to show for payers and KOLs to support use of a next-gen once a generic RUX is available? Thanks.

Reid M. Huber - Incyte Corp.

Analyst

Yeah. Hi, Brian. This is Reid. I'll take your question. You're right. We did publish some data on a sustained-release formulation of ruxolitinib, and there's actually some intellectual property around that as well, which has recently been locked down. Those are important efforts for us, and they really dovetail with the remarks that Steven just had on the combination work. In some respects, that is kind of the first line of the lifecycle strategy is to try to work on a more optimized pharmacokinetics profile of ruxolitinib that's beneficial in terms of patient usage but also potentially brings important benefits in terms of their cytopenias or even the benefits that ruxolitinib achieves in terms of spleen volume reduction and symptomatic improvement. So, that's sort of the first leg. I think the combination study that Steven outlined is the second leg. And just for completeness, the third leg is a continued strong interest in active research programs we have internally, both fully in-house and in collaboration with academic and company partners to try to identify new targets in the space that could be approached as, frankly, to obsolete ruxolitinib one day. And so, these are all three active efforts within Incyte and I think help to underscore just how significant the commitment is that we have to MPN patients.

Brian Abrahams - RBC Capital Markets LLC

Analyst

Thanks so much for the color.

Operator

Operator

Thank you. Our next question is coming from Katherine Xu from William Blair. Your line is now live. Yu Katherine Xu - William Blair & Co. LLC: Yeah. Hi, good morning. I just have a question on pemigatinib. Can you comment on the intermittent versus continuous dosing of the drug in both cholangio and in bladder? And then, are you confident in terms of efficacy that you could attain with this increase in dosing? And then, on the safety side, what would you expect with a more intensified dosing mechanism? And mechanistically, understanding that these are FGFR2 or 3 mutation-driven cancers, but does it make sense to find a combo partner to further increase the efficacy in these patients? Thank you.

Steven H. Stein - Incyte Corp.

Analyst

Katherine, hi. It's Steven. Thank you for your question. It's a good one. So, in terms of the dose we netted out at the end of Phase 2 trying to weave the therapeutic ratio between efficacy and safety, we had come up with a 13.5 milligram two weeks on, one week off dosing regimen, which many competitors at the time were doing as well, given the tolerability profile as regard to hyperphosphatemia, GI side effects, et cetera. Our cholangiocarcinoma dosing regimen, as you've seen, is the intermittent one, 13.5, two weeks on, one week off, with the efficacy we just showed at ESMO and just spoke about. In the interim in FGFR3 mutated bladder cancer, the lead competitor there, the J&J compound, had switched from intermittent dosing to different continuous dosing regimens and had shown incremental improvements in efficacy from the mid-20% range up to the low 40% range and had filed earlier this year, it achieved breakthrough status. And that's the way they're doing their program in bladder cancer. So, what we've done in bladder cancer is switch from intermittent dosing to continuous because, again, we look like we have a similar response rate with intermittent there, and we're just beginning that continuous dosing journey and should enroll fully our study at some point next year, as Hervé said in his remarks. What we'd want to see from that is an incremental improvement in efficacy like they did in bladder cancer. Your safety question is pertinent, though. If you look at discontinuation rates between intermittent regimens and continuous regimens for our competitors, they almost double. So, you can go upwards of a 20% discontinuation rate, where you do continuous dosing. And obviously, that'll have to be watched because you want patients to stay on therapy. You want durability of…

Operator

Operator

Thank you. Our next question is coming from Tyler Van Buren from Piper Jaffray. Your line is now live. Tyler M. Van Buren - Piper Jaffray & Co.: Thanks and good morning. In the release, you specifically mentioned a positive enrollment of the GRAVITAS trial. So, as we think about the enrollment as a positive indicator of potential market uptake, could you elaborate on some of the factors driving enrollment in that trial? And then as a follow-up question to that, I believe the long-term Jakafi guidance includes the smaller acute steroid refractory indication. So, as you think about the expansion of that into both chronic and steroid-naïve in the broader GVHD opportunity, could you help us put some numbers around the magnitude of that potential opportunity in terms of sales as you guys currently think about it?

Steven H. Stein - Incyte Corp.

Analyst

Tyler, hi. It's Steven. I'll go first and then hand it over to Barry. So, just to mention, the GRAVITAS-301 program that you referenced is with itacitinib, our JAK1 inhibitor. And then you turned over the rest of the question to RUX, so, I'll let Barry address that part. But for steroid-naïve acute, I think it's numerous factors. We've been really encouraged by the rapidity of enrollment and the enthusiasm around it. And I think it's related to the fact that there's a large unmet need in this area with a disease that can be of high morbidity and actually high mortality at six months, so there's that need to address. Plus, now the knowledge through numerous publications that JAK inhibition is highly effective, so people want to get on to these studies and have it tested. And I think those are – and then the global nature of the way we're conducting the study across the U.S. and Western Europe as well as some Japanese enrollment. So, those are all driving very encouraging enrollment and we're really happy to see where that is. I'll pass it over to Barry for your commercial question.

Barry P. Flannelly - Incyte Corp.

Analyst

So, Tyler, I think you were asking two separate questions. One is that the long-term guidance that we have on Jakafi, which includes acute steroid-refractory GVHD and chronic steroid-refractory GVHD as well as ET, and that brings us to the $2.5 billion to $3 billion guidance that we have given before. In terms of itacitinib, obviously, it would be used mostly in what we're currently studying in treatment-naïve acute GVHD and treatment-naïve chronic GVHD, and globally, so that is a global product. So, that is separate from our guidance on Jakafi. So, globally for itacitinib, we see about 15,000 patients that would have both treatment-naïve acute GVHD and treatment-naïve chronic GVHD. And then you can do the numbers from there. And obviously, we haven't done pricing and other forecasts around that. But we know what the opportunity is, it's bigger than the – perhaps the steroid-refractory setting and we'll take advantage of that. Thanks. Tyler M. Van Buren - Piper Jaffray & Co.: Thank you.

Operator

Operator

Thank you. Our next question is coming from Ren Benjamin from Raymond James. Your line is now live. Reni Benjamin - Raymond James & Associates, Inc.: Hey, good morning. Thanks for taking the questions and congrats on the quarter. Can you talk us, or walk us through kind of your thoughts regarding the data from competitors in terms of pemigatinib and how you're viewing that data in terms of indications perspective where you're actually competing in things like bladder or do you think certain indications are going to be free and clear? And related to that, can you talk about the importance of Foundation Medicine companion diagnostics or companion diagnostics, in general, and how that could impact your uptick?

Steven H. Stein - Incyte Corp.

Analyst

It's Steven, I'll go first. Others may want to add to my comments. I think when you start getting more competitors, it's sort of validation of that you're chasing a target, although there is no approved FGFR inhibitor yet but that's recognized as an oncogenic driver, which you have compounds that are active, and you've seen activity data now in cholangiocarcinoma, which is FGFR2 translocated, FGFR3 mutated bladder. And in fact, a myeloproliferative neoplasm that we are studying as well, that's FGFR1 driven through an 8p11 chromosomal translocation. And then potentially other areas where FGFR may be a driver, but it's a little more unclear, because you're often looking at amplification rather than mutations. So, in terms of talking directly about competitors, which I won't do, but it's interesting that the field is as busy as it is. That's encouraging, it's good for patients, and we can learn where others are ahead. And I just gave you the perfect example earlier of the J&J switch with their inhibitor from intermittent to continuous and getting that efficacy bump, which we can clearly learn from and catch up pretty quickly. So, we don't view bladder as gone in any way, we think we have a superb molecule, we're going to do the continuous dosing experiment. As I said, we should finish enrollment sometime next year and we want to be very competitive there with what we think is an excellent compound. In cholangio, our view is we're ahead of everybody else. And as we said with the dataset, we will take it to hopefully a regulatory filing next year. In terms of the companion diagnostic, the way it works from a regulatory point of view is one has to have that attached to your study. We're working with the lead developer in…

Operator

Operator

Thank you. Our next question today is coming from Christopher Marai from Nomura Securities. Your line is now live.

Christopher N. Marai - Nomura

Analyst

Hi. Thanks for taking the question. Maybe to follow up more on the topical RUX. So with respect to atopic dermatitis, could you perhaps comment on the potential size of the Phase 3 that you're going to be required to run? And then secondarily, any other safety studies beyond the typical Phase 3 that will be required for that? And then, secondarily on vitiligo, obviously, Phase 2 is ongoing. Is that a registration-worthy trial? And then I have a follow-up. Thank you.

Steven H. Stein - Incyte Corp.

Analyst

Yes, it's Steven. Christopher, thanks for your question. So, on the size of a Phase 3 program for atopic dermatitis, I alluded to it a little earlier. But the FDA requirements on safety are the main driver here. We'd need at least 1,000 patients' worth of data probably across two studies. It could end up being slightly north of that. The good thing is these studies are relatively easy to do and go really quickly, as you just witnessed from the baricitinib atopic dermatitis program. So, there's no concern there. We'll get the right size in and get the right safety database to do that. For vitiligo, we have a very well-constructed proof-of-concept study similar to the way we did atopic derm with the dose ranging, the right control, et cetera. Would that suffice? Your question was on a standalone for regulatory approval. It's somewhat unlikely in the derm space. You usually have to conduct the studies I just mentioned. But given that we will have a large safety database from atopic derm, it's certainly something we would discuss, depending on the results. But just to manage expectations, the likelihood is that we would have to conduct, as Hervé said, the vitiligo Phase 3 program to get it across the finish line there. Thanks.

Christopher N. Marai - Nomura

Analyst

Got it. And then, just a follow-up, thinking on about the commercialization for pemi, it's obviously, as someone else brought up, outside hema onc and in solid tumors. I was just wondering, could you remind us of the option that you have to co-promote capmatinib and how that option to co-promote might work into plans to also commercialize or set up commercialization of pemi? Thank you. Hervé Hoppenot - Incyte Corp.: Hervé here. I will answer. On the worldwide basis, we have no intention to go into co-promotion of capmatinib at this stage. I think the contract we have with Novartis on the capmatinib gives them the right to promote it. And so, that's not part of the plan. I would say, on hematology versus oncology, you have – depending on the countries, you have a separation of the two specialties on that. I mean most of them are practicing in the same buildings, in the same hospital. So, you can imagine that there is from hematology commercial organization already synergies for launching an indication in oncology, like for example, cholangiocarcinoma, if it is the first to come up. Cholangiocarcinoma is relatively rare. So, it's an indication where we believe we could fairly easily be promoting it by ourselves in a way that will not involve a very large increase of our sales force. So, depending on other indications that would be coming after cholangiocarcinoma, I think bladder cancer will be a specific different type of customer base, in fact, with some of them being in the urology department. So, we will have to address as we go. My experience with hematology-oncology and the mix of products in both specialties over a number of countries – a large number of countries over a number of years is that there is a lot of ways you can organize it geographically or by specialty, depending on the density of your customer population. And that's probably what we will be doing.

Operator

Operator

Thank you. Ladies and gentlemen, in the interest of time, we have one final question from Carter Gould from UBS. Please proceed with your question.

Carter Gould - UBS Securities LLC

Analyst

Good morning. Thanks for squeezing me in. Dave, congrats on your retirement. I want to ask on the RUX program in AD, I want to understand better a little bit the stage gate to starting some studies in pediatrics. How do you and I guess FDA feel with the safety profile potentially in that population? And I guess, how critical is that to how you see the value creation opportunity in AD? And then as a follow-up, Hervé, I appreciate your comments around the relative spend coming from early-stage programs. Any intention to increase your disclosures around where R&D spend is coming today?

Steven H. Stein - Incyte Corp.

Analyst

Carter, I'll go first and then Hervé will take your second part. It's Steven. So, the RUX program in total will look at patients initially from 12 years of age and above with mild to moderate atopic dermatitis. And that will address the vast majority of that population. In terms of the pediatric set in the 2 to 11-year age gap, per the definition, that is what we are discussing with the FDA at the moment. It's an area we'd like to address. We need to just work out with them what they would consider safe dosing in terms, again, of the therapeutic ratio. And that should follow thereafter. But the program should start initially in ages 12 and above and that will address most of the mild-to-moderate population with which we want to go after with the ruxolitinib cream. Hervé Hoppenot - Incyte Corp.: So, on your question about R&D allocation, obviously I think it's an important question, in fact, because as you can see, there are a lot of aspects of what we do that is very much quantified and rational and based on our projects. And the more clarity we can give on how resources are allocated, I think the better it is. So, we are looking at what is the sort of the norm in our industry. So, we have been looking at how other companies have been giving more clarity on their R&D allocation and we will be considering doing some of that or all of it in the future when – at the time we are reporting next year.

Carter Gould - UBS Securities LLC

Analyst

Thank you.

Operator

Operator

Thank you. We've reached the end of our question-and-answer session. I would like to turn the floor back over to management for any further or closing comments. Hervé? Hervé Hoppenot - Incyte Corp.: Okay. Thank you for your time today, for your questions. We look forward to seeing you at upcoming investor and medical conferences including at ASH. But for now, we thank you again for your participation in the call today. Thank you and good-bye.

Operator

Operator

Thank you. That does conclude today's teleconference and webinar. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.