Rigel Pharmaceuticals Inc at JPMorgan Healthcare Conference

Jan 16, 2020 PM UTC 查看原文
RIGL - Rigel Pharmaceuticals Inc
Rigel Pharmaceuticals Inc at JPMorgan Healthcare Conference
Jan 16, 2020 / 03:30PM GMT 

Corporate Participants
   *  Raul R. Rodriguez
      Rigel Pharmaceuticals, Inc. - President, CEO & Director

Conference Call Participants
   *  Tessa Thomas Romero
      JP Morgan Chase & Co, Research Division - Associate

 Tessa Thomas Romero,  JP Morgan Chase & Co, Research Division - Associate   [1]
 Welcome, everyone, to the Thursday morning of the 2020 JPMorgan Health Care Conference. My name is Tessa Romero, and I'm one of the biotechnology analysts here at JPMorgan. On behalf of myself and the team, I'm pleased to welcome to the stage Rigel Pharmaceuticals. And presenting on behalf of the company is CEO, Raul Rodriguez. Raul?

 Raul R. Rodriguez,  Rigel Pharmaceuticals, Inc. - President, CEO & Director   [2]
 Thank you, Tessa, and good morning. Thank you for joining us. Thank you for -- to you and your colleagues at JPMorgan for inviting us again. It's a pleasure to be here and kick off the year in good fashion.

 So let me introduce Rigel to you. Some of you don't know us. I'll tell you a little bit more of the story for those of you who do know us. Some important forward-looking statements, you could read these on our website as well. Let me go to the story.

 There are 4 main key value drivers for Rigel, and as you see on this slide. And I'll take you through each of these, in particular what we accomplished in 2019. 2019, we advanced each of these in very good fashion, and we're very happy with the way the year went and certainly how the year ended and some important events coming as well based on this accomplishments of 2019.

 First, on the left here of the slide, we're growing TAVALISSE sales in ITP. I think that is the cornerstone of the company in terms of the near-future opportunity. And we even had very good progress in 2019. We ended the year with $13.8 million in sales -- net product sales in Q4. That's a 90% increase from the equal quarter last -- prior year and 18% in year-over-year and quarter-over-quarter growth as well. We're very happy with that. In total, $43.8 million in net revenue for the year, so great accomplishment in our first full year of being on the market with this product.

 In addition, one thing we wanted to highlight here is our persistency. This is the fourth month refill rate is what we measure here. And the reason we do that is that the label says, "Try the product, doctor, for 3 months. If you don't see a benefit, you should stop." So we think of the fourth month refill as if you're getting a refill that month. It's because you're seeing a benefit. You wouldn't have done that otherwise. So we like monitoring this fourth month refill to see how we're doing there.

 When we launched early in the launch phase of the product, we were at 45%, then it was 50% last year and now it's 54% at the end of last year. So nice, steady climb in that, driven by 2 main things. We think doctors are just better at using the product. This is a completely new product in an indication that there hasn't had a new product in over 10 years. And it takes some education to -- in educating them on how to use the product and how to use it well, how to dose titrate up, sometimes down, how to manage AEs, what to expect. And that helps drive that, in addition, beginning to bleed into earlier lines of therapy. And I'll tell you a great deal about that in a minute.

 The other -- the next value driver is capturing value in the global ITP market. In the 2019 and last 16 months, we've done 3 ex-U. S. deals with 3 really excellent companies in the major geographies outside of the U.S. We did deals there in Europe in particular, the largest market outside the U.S., and they are in that market. We filed the MAA ourselves. And we're happy to announce that last week, we received approval in Europe. So this is the second geography with where fostamatinib TAVALISSE is approved. And our partner, Grifols, is gearing up for that launch. I'll give you a little more information on that.

 In addition, our partner, Kissei, in Japan and Asia, has launched the Phase III trial to get the product approved in Japan. So very happy with that progress. We, ourselves, filed the NDA equivalent in Canada, the NDS. And we think that we'll have an approval towards the end of this calendar year. So great progress along those, and I'll tell you more about those in a second.

 Perhaps an even bigger opportunity for Rigel is warm autoimmune hemolytic anemia. This is a very -- almost the excellent -- an excellent comparable condition to ITP. And in this area, we launched the Phase III trial in warm autoimmune hemolytic anemia in 2019, and we've made very good progress. We've opened up sites in almost 22 countries now. We're targeting 100 sites, and we opened up close to 50 sites in the last 3 months, so a big increase in the number of the sites opened and recruiting patients.

 Consequent to that, we have had a nice acceleration of enrollment. We're at 20 patients now and 15 of those enrolled in the last 2 months. If you open lots of sites, patients come and follow. So very happy with the progress there on warm autoimmune hemolytic anemia. I'll tell you a bit more about our future plans in 2020.

 In expanding the pipeline, 2 key assets for us: an IRAK1/4 inhibitor and a RIP1 inhibitor are in Phase I. These are 2 of the most attractive immune targets in biopharmaceuticals today. And we're very happy to have 2 very attractive molecules in each of these areas. And I'll tell you what our plans are for 2020 for these 2 areas. These all -- all these opportunities are really excellent opportunities in that they're very large. ITP is a $1 billion market currently, and growing, dominated by the 2 TPO agents: Amgen's Nplate product and Novartis' PROMACTA product as well as some Rituxan sales.

 Outside the U.S., the ITP market is a little smaller, about $800 million, but a very attractive opportunity as well. AIHA, warm AIHA, we think, is about $1 billion opportunity. So a very substantial opportunity but equal to the size of the ITP market. And then the other pipeline programs offer us tremendous opportunities in the future.

 Let me go to TAVALISSE and focus on ITP for a few minutes, if I may. So we -- this is the approved label, the approved indication for TAVALISSE. It's approved for the treatment of ITP, chronic ITP in adult patients who have had an insufficient response to a previous treatment. So it's a very broad label, something that we very much wanted. This allows us to compete in ITP across the board. ITP is typically treated by a steroid as a first line of therapy. And after that is where we are allowed to compete, and this allows us to do exactly that. It is very much the indication we were seeking when we filed for approval.

 ITP is an autoimmune disease. The body produces antibodies against its circulating platelets. These platelets are then destroyed by macrophages, which signal through SYK kinase. TAVALISSE, our product, inhibits SYK kinase function and therefore stops this autoimmune destruction of those platelets. And as a consequence, platelets rise. People with ITP have some very serious issues of severe bleeding, fatigue, bruising, fear of cerebral hemorrhages. So it's a very serious condition in the U.S., about 68,000 patients in the U.S. The prevalence rate is comparable in other countries.

 In the U.S., about half the patients are watched in any 1 year. About 1/4, a little less than 1/4 are just on steroids. And a little more than 1/4, close to 19,000 patients, are treated beyond steroids. That's in 1 year. Over the course of several years, there's a lot of circulating amongst these buckets. And in totality, the 68,000 is really the population we're going after as an addressable market. Where we're excited about TAVALISSE in ITP is that it directly targets the underlying pathophysiology of ITP, that is that platelet destructive process. And this is a very different product than what's available currently.

 Beyond steroids, the 2 main methods of treating ITP are: Rituxan, which is a broad-acting immunosuppressant; and the TPO agents, which stimulate platelet production, that is they don't address the destructive process, they just pump up more platelets and try to overwhelm the destructive process. And while that works, it also is off-mechanism and creates some issues. So we're very happy to offer, with TAVALISSE, the most targeted product that addresses the underlying cause of ITP and a unique opportunity after more than 10 years of nothing else being approved for the market.

 An important chart here. This is what we use with our doctors to discuss our product and introduce our novel mechanism of action. One of the things that we wanted to accomplish with our product, as we introduced the product 18 months ago, is to tell doctors about the product, tell them about the mechanism and provide education on how to use the product successfully. What patients, what dose to start 100 milligram and then titrate upward to 150 milligram, how to manage some AEs, et cetera. That 18 months really -- did that successfully, and we're beginning now to make a little bit of a pivot here. Now we're beyond introducing the product. We're discussing why they should use our product in second line.

 This is a data we presented at the ASH conference about a month ago, where we show that in second line, we have a 78% response rate, which is equivalent to the perceived response rate of the TPO agents and then actually it's a bit higher if you look at their clinical data. So a very good response rate in patients that are in second line of therapy. That's a very important segment to begin to penetrate because second and third line are a very large patient population. About 75% of the addressable market is in second and third line. So it's important that we penetrate that. And I think this data begins helping craft the argument for doing exactly that.

 Those patients also have a higher response rate and a higher persistency. So that'll also help drive the persistency of the product, that is the longer -- how long patients stay on the product. And that's very helpful as well. And so we'll begin continuing to discuss this with doctors as we discuss the benefits of the product.

 One of the things that's attractive about TAVALISSE is that the AE profile is quite manageable. The most common AEs are diarrhea and hypertension, all reversible and almost all are grade 1 and mild to moderate. We have no thromboembolic events with our product in our Phase III program and extension to that Phase III program. That's a very important thing because it differentiates us from the TPO agents that raise platelet counts independent of the disease process and, therefore, may be a concern to some doctors. And we're highlighting some of the differences.

 For example, perhaps in patients with risk of thromboembolic events, you ought to consider using TAVALISSE preferentially, and beginning to craft that argument and beginning to have the discussion with doctors that allows us and them to begin rethinking how they treat this disease. They've been treating it for 10 years in the same way, and now it's the time for them to begin challenging and turn certain aspects, say, people with thromboembolic risk. But that opens the opportunity to have a broader discussion as well. And with data showing us to be equivalent, I think that allows us to have that argument and to be a successful -- to be considered in that second and third line of therapy where we want to be. Just to remind you, we have treated over 6,000 patients with TAVALISSE, so really an extensive database for the product on the safety side.

 So in addition to using that 78% data from our previous clinical trial, we're also conducting, on the left side here, other data to help us reinforce that positioning, real-world data, where we look at our own data, look at data from various partners of ours to see how the product is doing in second and third line. And we'll be publishing that in the form of case studies and other publications to help us have that discussion with doctors.

 In addition, we're launching an observational study, where we'll look at patients that are in second line to see how our product progresses there and the utility of the product. It will be an open-label study, and it will allow us to generate data on a continual basis, maybe every 6 months as we report updates to that study. But I think all of this will help us reinforce the utility of TAVALISSE in second and third line and to help us make that argument successfully in this next stage of the product.

 To do so, we have a highly experienced commercial and medical team. We're expanding our sales force slightly to 41 reps from 35. We launched it with 30 about 18 months ago. 6 months into it, where we looked at it and said, "Look, there's about 5 other pockets that we're just not getting to adequately." And we added 5 reps early last year. They were very good adds. They contributed substantially to the product. And now we're adding 6 more to help us continue to do that. I think that's a very attractive thing to do in the territories that we are adding them, where it will really help us now that we're a bit larger product.

 We also do a great deal of peer-to-peer education in the form of a speaker bureau presentations. These are doctors that have colleagues in their area and they speak about how to treat ITP and how to use TAVALISSE. Doctors meet with our reps and get a lot of very good information. But when they meet with their own colleagues on how they treat it, that is a different level of influence. And it's particularly important in some geographies where access to doctors is more challenging. So that's a key marketing strategy for ourselves.

 In addition, we have an excellent market access plan. We have about 92% approval rate, so we're very pleased with that as well. So very happy with where we're going with ITP in the U.S. Outside the U.S., as I mentioned, we've made great progress. We received approval last week for a label that is equivalent to the TPO agents' label, and that's a very good place to be. So now we'll have the same process, starting in Europe.

 Our partners, Grifols, is planning on launching fostamatinib in Europe in the middle of this year and beginning in the major countries in Europe, so we look forward to that. Economically, we will receive a $20 million milestone payment from Grifols this quarter and should begin to see royalty payments from them beginning in the second half of the year. Kissei, as I mentioned, has launched the Phase III trial in Canada. We submitted the NDS.

 I'm going to just say a quick word in the -- these 3 deals have generated $68 million in upfront cash for us, which is very useful. We've also received -- we'll receive nice-sized commercial payments and royalties that are very attractive that we think are profit sharing-type of economics. It's an $800 million opportunity in Europe, and I think we'll capture about half the value of our product in those territories because of our partners. So I think we're in very good shape in Europe.

 I want to touch a little bit on autoimmune hemolytic anemia. So warm autoimmune hemolytic anemia is basically the same disease as ITP. The body produces antibodies against its own red blood cells. Those are then destroyed by macrophages, signaling through SYK kinase. It's very much the same story. These patients are treated with steroids, some Rituxan use and then there's nothing else for them. So there's a tremendous opportunity here. It's very much like the ITP market before the approval of the TPO agents. And so because there's nothing approved, we think there's a great medical unmet need. And it's highly synergistic to what we're doing in ITP. It's the same product, same dose, same mechanism of action. So as we had interactions with clinicians today, all that knowledge, all that education is transferable to when we have approval for AIHA. So we're very excited about this opportunity.

 We had Phase II data that we presented at the ASH meeting here on the left, 25 patients showing a 44% to 48% responder rate. Looking at hemoglobin and taking hemoglobin above 10 delta of 2 from baseline, manageable AE profiles. And this year, we launched an 80-patient placebo-controlled, randomized trial, again, looking at hemoglobin levels and now with a durability measure. So we expect to have top line results here by mid-'21.

 Let me just give you a little update on how things are going in that trial. Very good progress. We're planning on opening 100 sites for 80 patients. That's how important this indication is for us because we want to be the first to be approved in warm autoimmune hemolytic anemia. So good progress, so far. We had 15 patients enrolled in the last 2 months. We're scheduled or on track to complete enrollment as planned by the middle of this year. And we will have a first-mover advantage because of that, so we're very happy with the progress in warm autoimmune hemolytic anemia.

 Let me shift over to the pipeline. SYK inhibition in the form of fostamatinib, really an excellent model. It's immune -- central immune signaling pathway, and that's what our research group is very good at finding. We've been very successful in finding -- identifying molecules against all the targets that you see on this slide: the first to put a SYK inhibitor in the clinic, the first to get it approved and the first to get it marketed. So a couple of JAK inhibitors that we discovered in the hands of our partners at Aclaris and AstraZeneca. A couple of oncology targets, too, AXL and MDM2 in the form of partnerships there.

 For ourselves, we have 2 new attractive assets: IRAK1/4 and RIP1. They're attractive because they address key immune signaling pathways and have a wide range of clinical opportunities. Some large indications, some small, some that we can go forward ourselves, some that are best done by a partner, some that are best codeveloped, and I'll tell you what our plans are. And so it gives us a lot of options with these 2 programs that are basically at the same stage, in late Phase I study.

 As I mentioned, much like SYK, IRAK1/4 and RIP have broad opportunities. And you see here some disease areas that are very large, rheumatoid arthritis, even Alzheimer's. Some of them are smaller, GvHD, ITP, AIHA that are much more narrow indications that, if commercially, may be a more of interest to us.

 IRAK1/4 is -- we have 835, which is an IRAK1/4 inhibitor. It blocks inflammatory cytokine signaling from the toll-like receptor in IL-1 family of signaling, and so it has broad utility. And we have a molecule here that has a very good PK, a very good safety profile. And this year, we published this LPS challenge study, which is a proof of mechanism study to show are we -- is this product working as we think it -- want it to work.

 So here, you take normal human volunteers, usually it's college-age students. You give them this protein, LPS, which stimulates a substantial increase in pro-inflammatory cytokines. And then you see if your molecule is able to diminish that versus a placebo agent. And you see on these slides -- and there's several. There are about 6 different cytokines you track, 2 of them are the most known here, TNF and IL6. You see substantial reductions in those inflammatory cytokines. And that's exactly what you want to see in the use of this molecule in chronic diseases that you're able to do that.

 Now this is an artificial condition. It's normal volunteers. You caused the insult and then you cure the insult. It's an acute study. But it shows us that we're doing exactly what we want to do on a more chronic basis. And this molecule is able to accomplish that. And that's really exciting because in humans, in particular, this adds a great deal of value to this program.

 For our RIP1 inhibitor program, this is a really interesting program as well. It addresses inflammation from the necroptosis side. So as cells die and when they die in a high level, they spill their contents into the environment, which causes a rapid inflammatory response. And it's thought that this tissue damage caused by this inflammatory response underlies many inflammatory diseases and some neurodegenerative diseases such as Alzheimer's and ALS.

 R552 is a systemic RIP1 inhibitor, and it has very good PK, very good linear exposure. And we think we have a once-a-day drug here so half-life of about 15 hours. So a very exciting program. We've done large number of animal models. Here you see animal data from joint inflammation as well as skin inflammation showing a very good response to this molecule.

 So we have 2 programs, both in Phase I. With IRAK1/4, Pfizer is ahead of us. They have RA data that they put out last quarter, showing good results with their IRAK4 inhibitor. We have an IRAK1/4, which is more broadly immunosuppressive, and we think may have broader utility than that. With the RIP1 program, we're behind Sanofi-Denali. They have an attractive molecule on the clinic for Alzheimer's, a CNS molecule. And they just started looking at the systemic molecule, a really attractive asset as well. So we have 2 really attractive assets that what our objective are is to codevelop and copromote one of these or both of these assets with large pharma partners in this calendar year.

 There's just so much opportunity here, large and small, that the best way of exploring the utility of these molecules is with a partnership such as that. So we look forward to telling you more about that as the year progresses.

 Let me skip this as -- for the interest of time. So we had a very good year last year, very good year in terms of TAVALISSE growth. And you see on this chart, since launch, a steady upward climb in terms of our revenue. We're very pleased with the uptake of the product from -- for doctors. You see the bottle counts there as well, we added some numbers. A few bottles went into inventory last quarter, but not too different than prior quarters. The numbers of the weeks in inventory is about 3, which is kind of where we've been most of the year last year. So very steady, good climb.

 Q1, as you see there a little bit, always the most challenging quarter, simply because of insurance resets and Medicare donut-hole issues. We don't expect anything different this quarter than last year. So we're looking for acceleration after that as we had last year. So we're very pleased with what happened last year and most likely we'll be replicating something like that with a slower first quarter then acceleration after that.

 We ended the year with $98 million worth of cash, a good position. To remind you, we're going to add $20 million as we get the milestone from our Grifols partnership. So that's close to $120 million in cash. In addition, last year, in Q3, we put a credit facility in place with MidCap. We've taken a $60 million credit facility. We've taken down $10 million of that. So we have an additional $50 million that we can tap into with fairly, fairly low minimal thresholds. And so we're very pleased with the financial position that we ended the year last year.

 So let me take you through some of the key things that we're looking forward to in 2020. We're going to drive sales in TAVALISSE in ITP in the U.S., increasingly move into earlier lines, grow the commercial team and the awareness of our product with doctors. We're going to receive a $20 million milestone payment from our partner, Grifols, and looking forward to the launch of the product in the major European countries beginning in the middle of the year and then some royalty checks.

 On AIHA, complete enrollment by the middle of the year and then have the data by mid-'21. And then we're looking to put a copromotion, codevelopment deal in place for 1 or both of the SYK -- of the RIP1 and IRAK1/4 programs in place. And we'll also select the CNS RIP molecule sometime in the year.

 So I think it's going to be a great year for us. Thank you for your support. Thank you for your interest.

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