Rigel Pharmaceuticals, Inc. (RIGL) Earnings Call Transcript & Summary

Hi, everyone. My name is Denise Liu. I am an associate on the health care investment banking team here. So we're excited to be continuing the 44th Annual Healthcare Conference this afternoon, and it is my pleasure to introduce Raul Rodriguez, CEO and President of Rigel Pharmaceuticals.

Thank you, Denise, and thank you to our colleagues at JPMorgan for having invited us to present. I'm excited to be in front of you and sharing this story. First, some important forward-looking statements. These statements are also available on our website. If you would review this, I'd appreciate it. Let me tell you a little bit about Rigel. And I'd like to share with you our strategic plan going forward because I think it's what's driven us to get to this place where we are today, and I'd like to share that and then what our plans are going forward. Our strategic plan has 4 strategic objectives: grow the commercial business, in-license and add products to that commercial portfolio, advance the product pipeline in the clinic and maintain financial discipline. All of these pieces work together very closely. They're codependent on each other. And you'll see in this story how we've used it in the last 5 years to get to this point and what our plans are from now into 2030. So going a little back 5 years in history, really breathtaking a change from then to today. In 2020, we were a one product, one indication company, TAVALISSE in adult chronic ITP in the U.S. only. We had a very limited development pipeline. We were in a position where we were using cash on a regular basis as we sold products, as we developed some early programs as well. Fast forward 3 years -- 5 years later to 2025. We now have 3 commercial products, TAVALISSE, REZLIDHIA and GAVRETO, 4 different indications for these products. We have a development pipeline that looks very interesting, led by R289, Rigel's internally discovered IRAK1 and IRAK4 inhibitor that we're studying in low-risk MDS and yet having data that looks pretty promising at this point. And finally, we're profitable. We turned profitable in Q3 of '24. Since that point, we've generated $100 million in cash, a really good performance. We've grown the top line. We've shown financial discipline. We've developed programs behind it to sell into the future. And you see we've made very good progress to this point. Now going into 2030s, which is what I'd like to talk mostly about on this presentation, our plan is to continue that growth for our current 3 products, add additional products, maybe a little larger than the ones we in-licensed, acquired in the past, all in hem/onc, move forward with R289, our IRAK1 and IRAK4 inhibitor, which we're currently working on in low-risk MDS. And in the future, we may work at it in other areas or an inflammatory product like this or inflammatory modulating product like this as important bearing on a hem/onc indication. I think it's a fantastic growth in the company, in the market cap of the company, in the financial position of the company, in the commercial portfolio and in the pipeline. Here's a little bit of a story in terms of the sales history of the company. We are very successful in growing the sales of the company. We grew 35% from 2022 coming out of COVID to the midpoint that we're guiding now at $260 million. But what's exciting is what's coming in the future, 2030 and beyond. As R289, our IRAK1 and IRAK4 inhibitor, goes through its development and registrational program in low-risk MDS and subsequently in other indications, those are not small indications and opportunities. That's multi-hundred million and potentially billion-dollar opportunities. So again, an inflection will come with this company in the next 5 years. That's no less important than what we've already seen in the first -- last 5 years. So let me tell you a little bit about each of these 4 strategic objectives, growing the commercial business. We've done that quite well, as you see here. And 2025 was really a stellar year for us. We grew the commercial business substantially. As you can see here, almost $90 million of growth in sales, tremendous. Every quarter was a record quarter for that quarter. And as you see here in Q4 of 2025, 41% growth over Q4 of last year. stupendous growth. And really, that growth was across all 3 of our products, TAVALISSE. TAVALISSE we launched in 2018. I'll tell you a little bit more about this product in a minute. And now we're still seeing tremendous growth with 47% growth in this product. It's great reaching $45 million in sales for this product. It's a great opportunity. GAVRETO, we acquired this product in 2024. It was previously sold by Genentech, Roche via license from Blueprint Pharmaceuticals. At the time of acquisition, it was selling about $7 million a quarter. We acquired it, focused on it, educated doctors about it, and now sales are over $10 million. Really a great performance for this product and at Rigel for really a little bit more than a year. And finally, REZLIDHIA. We in-licensed this product from Forma Therapeutics in 2022. It's for relapsed/refractory IDH-positive AML. And already, we acquired the product, completed the regulatory path, got it approved ahead of schedule, launched the product and already it's grown to nearly $10 million a quarter, substantial growth from a year ago, and there's more coming. I'll tell you a little bit each of these opportunities in sequence. So TAVALISSE. TAVALISSE is indicated for the treatment of adult chronic ITP, which is an autoimmune disease where the body destroys its own platelets. So these patients have very reduced platelet counts, and they live in constant fear of bleeding or bleeding episodes, bruising, fatigue are chronic things that they endure. There are about 81,000 adult chronic ITP patients in the U.S., 37,000 or so of them are basically watchful waiting. They have some form of remission or a mild form of disease. They clearly have ITP because their platelet counts are greatly reduced from normal. Eventually, they will need therapies. First-line therapy is typically a steroid. About 20,000 patients or so at any one time are on steroids, but eventually, they need other things. And that's where we're indicated for patients that have already gone through steroids in second line or beyond. That's about 24,000 patients. It's a good patient population that we're looking at there. Now when we launched the product, we launched it into a market that was pretty well established. The TPO agents that are commonly used here, there's 2 main ones, Nplate and Promacta, they stimulate platelet production in the bone marrow. And they were pretty successful. They were ahead of us by about a decade. In addition, Rituxan is used pretty commonly, which reduces B cell counts and has a benefit in this area. So we were used in highly refractory patients, patients in fourth and fifth line primarily after those 2 agents. And that's where we were initially during launch. But over time, as clinicians become more familiar with the product and more used to using it and having some success with it. They now use us across the board. We've had great entry into third-line therapies and even some in second-line therapies. And so really across the board is where we're being used, which is fantastic because you see by these numbers, second and third line have many more patients than fourth or fifth line. And importantly, beyond that, the earlier you treat with this product, the better your results will be. So if you use us in fifth line, you may get a 50% response rate. If you use us in third line, it's 86%. If you use us in second line, it's more like 94%. Those are excellent response rates. So once we are able to convince a doctor to try us in an earlier patient, they get great results. And then they tend to want to use it again. Now the other benefit of the product is once you have a positive result in this -- with this product, you tend to keep that positive results over the long term. So the durability of it is actually quite good. Every patient that we have this quarter that are succeeding on the product is almost certainly going to be with us next quarter. So it's a good way to build a business where you're building on what's coming in from the prior quarter. So we build and grow the business that way. And we've been very successful in doing so. One additional benefit we had this particular year is the Inflation Reduction Act, IRA. That helped close the large doughnut hole that precluded some patients from staying on the drug in Q1 of the year. So every Q1 prior to this 2025, we had some substantial number of patients drop out because of affordability of the product. We really couldn't help them, unfortunately. This year, with IRA, that has been addressed very successfully. That is it's much smaller number now, and it's smoothed out over the 12-month period, not just in January. The results of that is that many patients who would have dropped out did not drop out. And that helped us tremendously this calendar year. And it helped us in Q1, but those patients continued on therapy in Q2 and Q3 and Q4 and will continue hopefully on therapy in Q1 of this year. So we're excited about that. That was really a great outcome simply because the patient you'd least like to lose is one that's succeeding on your product. And that allowed this to happen. Those patients continued on therapy. I think a good contribution. We benefited from it greatly with regards to TAVALISSE. Let me go on to REZLIDHIA. REZLIDHIA is indicated for adult patients with relapsed or refractory AML with an IDH1 mutation. There are about 22,000 patients who are diagnosed every year with AML. And you may know, this is just a terrible disease, about 11,000 deaths every year from AML. It's a rapidly changing mutating indication where the illness is really unfortunate. Therapies work, but nothing works very long. IDH mutations are about 6% to 9% of all AML patients. So it's a minority of those cases, and they're well identified. Usually, by the time they get to the relapsed/refractory setting, they're genotyped, and so we know there are IDH1 patients. And this is a product that addresses that specific target. Significant unmet need for these patients, and we were delighted to see the data from the clinical trial that underlie the approval for this product. This is a Phase II trial, elderly patients, median age 71. This is a disease of elderly. And we saw a CR/CRh rate of 35%, which is a very good number, a little bit better than what was available with other agents at the time. And importantly, the durability of that response was 25 months, substantially better than what was available previous to this agent. So providing good response rates and much longer durability was something that we thought was very attractive about this product. So we're currently providing this product. We've had good success in launching this product and then the uptake of the product. And it's in the relapsed/refractory setting, but I'll tell you about some of the other things we're hoping to do in other settings that we're studying in collaboration with some partners. GAVRETO. GAVRETO is our most recent addition. It is indicated for non-small cell lung cancer and thyroid cancer for patients with a RET fusion-positive mutation. We like this product a great deal. One, it got us into a solid tumor market. And that's good. When we looked at our sales organization, they had substantial experience at other companies in the solid tumor space and lung cancer in particular. So we felt it was a product we could sell successfully. And obviously, the RET fusion patients are well recognized. They're difficult to treat. The results with RET fusion inhibitors such as this were very good and better than immune checkpoint and chemotherapy approaches that were used commonly. So we thought this was an exciting product to allow us to get into the market. It had already been on the market by Genentech for a number of years, but we thought we could do a bit better than that by focusing on it. As you can imagine, a product of $28 million, it's not that exciting to Genentech, but a product of $28 million with some growth potential, pretty exciting for Rigel. So we acquired it, we launched it. And so far, we've had good success with this product. It's an oral once-a-day agent. The competitor is twice a day, good response rates, good durability of those response rates. And so just a very nice product to have in the portfolio. Our focus internally is the U.S. market, the largest, most profitable market in the world. Outside the U.S., we've used partners to sell our products. So we partnered TAVALISSE with Grifols in Europe, where it's approved in most countries, with Kissei in Asia and Japan. It's approved in Japan. It's approved in South Korea. Other countries are coming and with Medison in Canada and Israel. Knight is our partner in Latin America, and we have an approval now in Mexico, and we're working towards approvals in other countries in Latin America. REZLIDHIA is still in development, but it's -- we partnered it with Kissei in Japan, South Korea and Taiwan and with Dr. Reddy's in Latin America. And you see these collaborative efforts give us nice royalties, nice milestones and also nice purchases of material, which we sell on a regular basis at a profit to them. So attractive partnerships. The partnerships are doing well. The products are selling well in these various countries, and we're reporting regular collaboration revenues. Let me go on to the second strategic objective in our plan, in-licensing and acquisition of products for our commercial business. Now what we're looking for is differentiated assets in hematology/oncology or related areas. We acquired REZLIDHIA in 2022, then subsequently acquired GAVRETO in 2024. And so we're looking for products similar to this, albeit maybe a little bit larger. We're a different company now than we were in '22. We're more profitable. We're cash generating. We have a strong cash position. And therefore, we want to have something even bigger than this. But we're looking at a wide range of things. In fact, this meeting is incredibly useful for us because we have a large number of meetings with companies at various stages of the deal process for looking at in-licensing something. We're looking for something that is late stage. By that, we mean having registrational data at hand. And the reason that's important is because we want to launch this product or products in '26, '27 or '28. '29, it begins a little bit, that's when we're beginning to shift our focus to our own launch of R289 in various indications like low-risk MDS. So it's something we want to launch in the next 3 years or so. And so late stage is a necessity. And if you have the data, then we can look at the data to assess the likelihood of this being a successful drug on the market. That means if it's NDA filed, that's fantastic. If the NDA is under review, that's good. If the product is approved and already on the market, also something we may be interested in. So late-stage opportunities where we could be on the market as early as '26, but really no later than '28. That's the objective here. And it has to be synergistic with our current capabilities in the hem/onc space because we want to leverage that capability. That is we don't want to expand the capacity a lot more, add new sales forces, for example. We want this to be highly accretive and pretty quickly. So it has to be in the doctor areas that we are interested and have presence already, hem/onc in both community or academic centers. So we're doing a lot of work here. And what this will allow us to do, if we have a drug that meets this criteria, just like GAVRETO and REZLIDHIA have, is that it's rapidly accretive. And therefore, our cash generation from our business is all that higher, allowing us to do even more in terms of pipeline development. Our third objective, advance our development pipeline. Here, let me say a few words about olutasidenib, our IDH1 inhibitor. We're focusing on strategic collaborations here. We put collaborations with MD Anderson, and they're looking at studies with this product in combination or as monotherapy in AML, including frontline AML, where we do not have an indication, MDS, high-risk and low-risk MDS, CCUS, CMML and MPN as well. So these opportunities, we're studying in this area. We should be generating data, perhaps not this year, but maybe next year, we'll be able to share the profile of this product and really elucidate the benefit of olutasidenib, our IDH1 inhibitor. Skipping one down, in MyeloMATCH, We recently announced That we're working with MyeloMATCH. they're going to be launching a frontline study in first-line AML and frontline MDS as well. And that will be a larger study funded by the NCI and NIH. That will be very beneficial because that's a market that we're very interested in. And then the Connect organization is studying this product in high-grade glioma. So a number of collaborative arrangements where we're hoping to really elucidate the product, publish information and perhaps get listings for these various areas. Our internal focus though is R289, our IRAK1 and 4 inhibitor, where we're evaluating the product in a Phase Ib study in lower-risk MDS. We've been granted Fast Track and orphan designation by the FDA, which is very helpful as we work on this product and try to move it forward. And as the year progresses, we'll share with you some of the other indications that we're interested in, tell you a little bit more about that. So IRAK1/4 in lower-risk MDS. So what's very interesting, and you may know this, as the last 10 years have progressed, the appreciation for the role of inflammatory process in driving cancers and hem/onc conditions has been more and more established. So that, for example, in low-risk MDS, it's understood that a very pro-inflammatory environment in the bone marrow is central to the growth of MDS. And therefore, the idea is, well, why don't we address that component? If we had an agent that was very effective in modulating the immune component in the bone marrow, that would be a really interesting approach and a very novel approach to treating potentially low-risk MDS. IRAK1 and IRAK4 allows us to do exactly that. IRAK1 and IRAK4 inhibitors inhibit the signaling of the toll-like receptor TLR as well as IL-1 family of signaling, reducing that inflammatory cytokines. And that's exactly what you would want to do in a disease such as low-risk MDS, potentially other diseases in hem/onc, where there's an important pro-inflammatory component to the disease. So this agent allows us to do something really, really novel that is suppress the inflammation in the bone marrow and restore normal hematopoiesis. These patients with low-risk MDS have an overburdened bone marrow by this inflammation and are unable to produce a normal count of red blood cells. By using this agent, we may be able to resolve that problem. It's the word. 289 is a prodrug of 835. In the gut, it converts fully to 835 and in circulation, 835 is the agent that does all the work. What we've shown with 835 is that it's able to block inflammatory cytokines in normal healthy volunteers quite successfully. Looking at -- we take normal patients, give them an LPS protein, cytokine storm occurs. What we've shown is that we're able to dramatically reduce that cytokine storm with 835. We've also shown that IRAK1/4 is much better than just IRAK4 in doing this. With IRAK1/4, you're able to completely inhibit major pro-inflammatory players like TNF, IL-6. IRAK4 only allows you to do that partially. So we think, especially for hem/onc indications, this is a fantastic tool to try this in low-risk MDS, are we able to achieve normal hematopoiesis with this product. And so we've launched a number of different trials, a trial that we're going to tell you a little bit about. But first, let me tell you a little bit about the landscape of low-risk MDS. As I said, MDS is a disorder of hematopoiesis, where the inflammation crowds out normal hematopoiesis. These patients are anemic, have other cytopenias and have a variety of other problems that ensue. Our goal is to limit transfusion dependency that is take transfusion-dependent patients and get them to transfusion independence or greatly reduce their transfusion burden. And to date, there are agents available for this indication, but there's substantial room for improvement. First line is typically erythroid-stimulating agent like an ESA. And failing that, they go on to an agent like luspatercept, which is a very successful product. This product sells $2 billion annually. Really a great product in terms of that sales level. However, it only produces about a 40% response rate. That is 60% of patients on luspatercept do not respond. So that's a real opportunity. Failing luspatercept, they typically go on to an HMA. The response here are even worse, 18% to 20% responses for HMAs. So again, agents are available, but boy, they leave a lot to be desired in terms of their efficacy. In some cases, even their AE profile is a little bit toxic. So we view the entire spectrum here from post-ESA pre-luspatercept as an opportunity after luspatercept, 60% patients don't succeed on that product or even afterwards, but that's a much smaller market. We're interested in the middle here, and we're interested in the left side of this slide because those are $1 billion-plus opportunities. One thing to say about this slide, there are about 12,000 patients, maybe a bit more than that with this indication. So a good number of patients available to treat here. So that's why these drugs are potentially billion dollar drugs. There are sizable opportunities in terms of this. I've already told you the mechanism of action is a good fit to the understanding of this disease. And I'll tell you a little bit about our Phase Ib study, which is what currently is underway. So this is an open-label, multicenter study being conducted in the U.S. And it has a dose escalation phase. I've shared the data with you from the dose escalation phase in a minute, but you dose up from a low dose to a more higher dose. We completed this phase of the study last year, we shared the results at ASH. Last year, we also selected 2 doses, 500 QD and 500 BID for a dose expansion. Here, we're going to add up to 20 patients in each of those 2 arms, and we'll see which of the 2 are the best in terms of moving forward. We'll pick one of those 2 doses this year in the second half of this year, and then we'll initiate a registrational study in 2027. Now the registrational study is still in discussion with FDA in terms of what that would look like. But almost certainly, we'll be taking patients that are transfusion dependent and getting them to transfusion independence as the primary objective, not too different than the Geron imetelstat product showed in recent study. So very similar to that. So it's a pretty straightforward thing that we have to do here. One other thing before I leave this slide, I want to point out to you, once we know the dose that we're going forward with, we're going to start a small study in the post ESA pre-luspatercept area and show how we do in that field because that's very interesting. Obviously, it increases the size of the opportunity if we show success there. So maybe about 12 months from now, we'll have the expansion phase data in hand, maybe a little less than that. And soon after that, we'll have this other additional post-ESA study. I think that really flushes out well what the opportunity is in the order of magnitude of what 289 could do in low-risk MDS, and we'll have a registrational plan in hand that we're going to start working on and getting it approved into the future. So that's an exciting time for this product. I think we have exciting data coming in later this year, exciting additional things to tell you about in terms of other areas we'd like to share with you. So here's the data that we shared at ASH. The patients that we studied were at the extreme right of that landscape. They were heavily pretreated elderly patients generally with high transfusion burden. The median age was 75 years old. They had failed previously 3 other therapies. 3 had an HMA, 76% luspatercept. ESA is about 73%. So pretty treatment refractory patients. As the clinician, Dr. Garcia-Manero of MD Anderson, stated at the podium at ASH, it's remarkable, and he used that word remarkable a number of times that you see any responses with these patients. I'll show you what we got in a minute. The safety profile looked good, well tolerated, low incidence of grade 3 or 4 cytopenias, low incidence of infections. I'd like to highlight in peach there, the 500-milligram QD in the middle and in the right side, the 500-milligram BID, where you see very small numbers of Grade 3/4 AEs in both of those cases. In fact, the things you see most frequently is anemia. Remind you, this is a disease of anemia, so you should see anemias because it's just a part of the disease. But a very acceptable safety profile thus far. I think well-tolerated drug. So we're pleased with those 2 doses, and that's one of the reasons we selected them to move forward into further study. We have here some PK analysis of R289 or 835 as it circulates. What we've shown is that at 500 milligrams or above, QD or above is where we have exposures that we think are good to see a response. And in fact, that's where we've seen responses. We've seen responses at 500 and above, and I'll show you some of those responses. But it's good to see this is where it is. The lower doses in that, probably not adequate. Exposures were low, and we didn't see any responders, not surprisingly. So it's good to have that correlated. Apologies for the complexity of this slide, but I think it's really telling. This is a chronological view of how we dose these groups starting at low doses and then going higher. What is important here is in the second bullet point. We had 18 patients that were transfusion-dependent and evaluable and the doses above 500, the dose that I said were about where you should see results. And within those patients, we had 6 or 33% responses in getting patients to transfusion independent. That's a pretty good result, especially considering the highly refractory nature of these patients. If you look at the 500-milligram BID dose group, we had 5 patients that were transfusion-dependent and evaluable. We had 2 responders there. So that's 40%. So that's the order of magnitude that we're talking about thus far. Now I can see this is a small data set as yet, and we're working to expand this data set substantially in the dose expansion cohorts, where we'll add at least 20 in each of those 2 dose groups, and we'll have that data later this year. So exciting to be able to show some benefit in these patients. The clinicians are excited. People that are involved with the trial see this as well. This is obviously showing some benefit, and it looks tolerable in terms of the safety profile. So it's a great place to be. A little bit more detail maybe in the hemoglobin levels. What you see here is that we're able to raise hemoglobin quite nicely, 2.9 to 6.1 in patients that had a response. And you want this to correlate with that, and it does. So it's useful showing that the patients have a reduction in transfusions or no transfusions for a while. And their hemoglobin goes up as they're being treated with the product. So it's very exciting to have this as a corollary. No doubt this will be probably a secondary endpoint in some future study. So in summary, well-tolerated drug studied in very elderly, very heavily pretreated patient population. And we had responses of about maybe 33% in patients who had adequate doses above 500 milligrams QD and who had -- were transfusion dependent. So it's a good place to be in terms of the product and future study. And it's exciting that it's in a category where there's substantial need as yet and where there's substantial opportunity commercially. Next steps for this drug in this area is to complete enrollment of the dose expansion and select which of the 2 doses to go forward into a registrational study, share the top line data with you sometime at the end of this year. And we also are going to start that post-ESA pre-luspatercept study to generate data in that very early setting because that will be an exciting data set to have. And we'll discuss with FDA what the registrational plan is and launch that study in 2027. Now this is a good place to start, but it's not the only place we want to go with this molecule. We think that the inflammatory cascade, a pro-inflammatory condition is important in a number of other hem/onc indications. And we're looking at quite a number of those in terms of where else do we want to go, where can we redeploy this agent. And as the year progresses, we'll come back and tell you a bit more about those opportunities, but we'd like to launch studies in those in sequence. Maintain financial discipline. Well, we've done that quite well. We've grown the top line, as you see here on this chart, almost very substantially on a quarterly basis, all products growing, TAVALISSE, REZLIDHIA and GAVRETO. And as the product sales have grown, what you see is pretty small growth in terms of the expense line. 40 -- low 40s is the number for the last 1.5 years or so, which is really very good. Top line keeps growing positively and strongly, discipline on the OpEx line. The result is we turned profitable, and we are starting to generate cash. You see we've doubled the cash position of the company to $154 million in calendar year '25. So we're in a strong financial position as a result of this, and we have a place to spend this cash, and I think we will. And I think it will lead to transformative products that are coming to the market sometime at the end of this decade. So our key priorities for this year is grow the commercial business, continue that growth, in-license another molecule to add to that to yield further cash flow in the future, near future, beginning perhaps as early as '26, advance the pipeline focused on 289 and in low-risk MDS, have that data, initiate the post-ESA study, discuss with FDA what's going to take to get this product approved and prepare to launch that registrational study, discuss with you other indications that we'd like to pursue with this. And finally, maintain financial discipline. We've given guidance. Our guidance is here, $275 million to $290 million in total revenue, comprised of $255 million to $265 million of product revenue and about $20 million to $25 million in contract revenue. And importantly, continue to be net income positive for the year. And that's important also because we still think we can have the ability to do that and still fund the clinical studies that we discussed today and other new studies in addition to that. Again, the company is in a very strong financial position, a very strong position in terms of the commercial business, strong position in terms of our ability to introduce new products from external sources and ability to generate a pipeline that I think will transform the company in the not that distant future. So thank you. I'd like -- I think we have about 5, 6 minutes.

If anyone does have a question, we have a mic to pass around. So just raise your hand. I can kick it off with the first question.

Sure.

It's great to see that R289 is progressing well. And you alluded to some updates in the near future about future indications and expansion. Is there any other detail that you can give us about expanding this product or mechanism beyond lower-risk MDS?

Yes. Well, I can't tell you the exact indications yet because that's coming. We're still working on that. I'll tell you some of the things we're interested in. We think that the inflammatory modulation that this product offers is unique. Interestingly, we are the only company in the clinic with a true IRAK1/4 inhibitor. That is we have a substantial lead in this area over anybody else. And other companies have studied IRAK4 inhibitors, primarily in inflammatory conditions, but not in hem/oncs yet. And I think that's a tremendous advantage that we have. And we have a tool, a molecule in 289 that I think is showing good safety, good exposures and initial positive results in terms of efficacy in one indication. So it behooves us to step on the gas in that and go into other indications as well. So what we're looking for is places where this mechanism is a good fit to that indication. There's quite a number of this. In addition, it has to be sizable. We're not interested in a $10 million or $50 million opportunity. We're interested in a multi-hundred million, billion dollar types of opportunity, and I think they exist. And we're interested in something where there is a medical need. There are some indications where this may fit, but it's such a well-served market that it may not be the right place to go with it. So there has to be a medical need for it. It has to be a good fit to mechanism in that indication. And there has to be something that is sizable enough to matter to us. So those are some of the criteria we're looking for, obviously, other areas, other things as well. But I think we put a lot of effort into thinking about this, and we'll be able to share some later this year in terms of what that might be. And soon after, hopefully, begin to launch Phase II studies in those new indications.

Are there any questions? Just to follow up on that. So you mentioned the significant unmet need in -- sorry, in lower-risk MDS and just how it's very targeted. It's the only one in clinic right now. How should we think about how it compares to other available therapies? And what should we focus on for the remainder of the year?

Yes. So in the landscape of low-risk MDS, as I mentioned, the approved agents are luspatercept and then imetelstat, the Geron product that was a recent approval and the HMAs. The response rates for luspatercept is about 40%. It's a successful drug. Like I said, $2 billion in sales is fantastic. But 40% is still not 100%, it's not higher. We have a very different mechanism than luspatercept. And that gives us some opportunity that in -- if we're able to show equivalence to luspatercept, we are competitive in that field pre-luspatercept. And that's what we'd like to show with that study that we're going to study. But in the post-luspatercept market, because we have a different mechanism than them, that's a very attractive market also because a large number of patients don't succeed on luspatercept and they need something else. That's something else that they currently use is HMAs, which I said 18%, 20% response rate. That's pretty low a response rate. I think we can beat that. Already in even more refractory patients, we're showing about a 33% response rate. So already, we're showing benefits that's well above what an HMA can give you. So we're really optimistic about our ability to show benefit and compete successfully along that spectrum, especially in the middle post-luspatercept, but potentially even in the pre-luspatercept market. And like I said, no one else has a mechanism such as this. And we believe and it's well established that the pro-inflammatory environment in the bone marrow is a central feature of routing out normal hematopoiesis. And if we can restore that, these patients will be able to produce normal red blood cell counts.

Just pivoting a little bit to the commercial products. I just was wondering if you could tell us a little bit about the drivers and your confidence in growing the 3 commercial products.

Yes. So we've had tremendous success in growing the commercial business. TAVALISSE, we launched it in 2018. So already, it's 7, 8 years into the market. But keep in mind, a couple of those years were COVID years where things were flat, we were not on in the field. The business in ITP, the other products also were flat. But coming out of COVID, we were able to really reestablish that growth. And it's because doctors are now more familiar with the product, we're using it more broadly. And that helped tremendously drive the growth of the product. And as I said, earlier line usage is important because earlier line usage means more success for that clinician. More success with that clinician means they're likely to use it in another person -- another patient in the future. Now one thing about this indication, it's a rare disease indication. So a typical doctor may have maybe 4 patients with ITP. It's not like breast cancer or lung cancer or prostate where there's lots and lots of patients. It's simply not like that. There's a very limited number of patients. So clinicians have just a few patients they're treating. So it's not even -- for any one doctor, probably once or twice a year is when they need a new agent. So you really have to be on top of this area to be able to intercede when that decision comes. And so that's taken years of establishing the product, lots of discussions, lots of clinician marketing. And -- but I think it's been a successful effort because now clinicians are comfortable with it. They talk about it as part of the usual paradigm for treating ITP, and that's taken years to get here. But we're benefiting from it now. Like I said, this past year, the IRA really helped us in terms of retaining patients that formerly would have dropped out. And that's been a good help for us, and we expect that to continue forward. So ITP is an important indication, and this product is central to our -- it's a cornerstone product to our success going forward.

Thank you. And I think we are out of time. So with that, I just want to thank the entire Rigel team for the work you do and a great presentation. Thank you, Raul.

Thank you so much, Denise.