Rigel Pharmaceuticals, Inc. (RIGL) Earnings Call Transcript

Good morning, everyone. Thanks for joining us on the final day of JPM this year. My name is Richard Meland. I'm with the banking team here at JPMorgan. And it's my pleasure this morning to introduce Rigel Pharmaceuticals. Presenting today, we have President and CEO of Rigel, Raul Rodriguez. We'll have some time for Q&A after the presentation. And with that, I'll hand it over to you, Raul.

Thank you, Richard and thank you to our colleagues at JPMorgan for having invited us today. It's a pleasure to present at your conference and again, thank you for very nicely organized conference and for scheduling the good weather, too. I appreciate all of that. So here are some forward-looking statements. They're very important for you to read. They are available on our website, so please read these. They're putting into this presentation. So Rigel is a hematology and oncology company. And we've worked very hard over the years to grow this company and make it substantially more. 2024 was probably our most important and it really -- and truly a transformational year for the company. And I'd like to tell you in this presentation why that's the case and why it sets us up so well for what's coming next in the future as we continue to grow our company. There are a couple of things on this slide that I'd like to take you through briefly in summary and then go into considerably more detail over some of them. The commercial business comprised of 3 -- now 3 approved products, 4 different indications. And I'll tell you about each of these in turn. But this has been a core component of the company that we've used to grow the business substantially. I'll share that with you today. Importantly, we're growing this business by not just expanding the growth of each individual product but by adding products as well. REZLIDHIA was in-licensed and then most recently, GAVRETO was acquired -- we acquired U.S. rights. So in-licensing and acquisition has been central to the growing of the commercial business. That growth of the commercial business coupled with financial discipline, has allowed us to do something really remarkable in biotech that is turn the corner and start generating cash. That's a fantastic place to be for a company like Rigel because now instead of relying on other sources of cash, we are generating our own cash. In fact, our cash position improved by about $20 million from end of year '23 to end of year '24, and we see that continuing into the future. However, it's just not that. We don't want to create cash. We don't want to be profitable for the front of being those things. Those are good things to be, though. It actually is because we have some really important opportunities that we want to move forward with and now we can do that. Two opportunities on the development side that I'd like to highlight and discuss with you in some length in this presentation. One is R289, our dual IRAK1 and 4 inhibitor discovered by Rigel and currently in a Phase Ib study in lower-risk MDS. And second, being olutasidenib, one of the in-licensed opportunities, REZLIDHIA, that we'd like to move beyond relapsed and refractory AML to other opportunities, which are quite meaningful, especially glioma. So you put all of this together, the company isn't truly a pivot point at this point. Growth of the commercial business, reaching financial breakeven and the future profitability, having important things to invest in, that, in turn, will take the company to the next level. These opportunities that we're going to discuss are opportunities which are -- where there is truly a major medical need and where these opportunities may in fact meet some of that need. So we're delighted to have the means and wherewithal and strategy to move those forward. I'll start with the commercial side of the business first and then take you into the development programs in the second. So first, let me just say a word about the sales of the company, which I said really remarkable. This year, we achieved $145 million in sales, just about. Every quarter this year, was better than its comparative quarter a year ago, as you see from this chart. Q4, in particular, 58% growth in this quarter over the same quarter last year, really a remarkable growth in the business overall at $145 million. That's about a 38% growth overall from the top line for the year-to-year, really impressive growth. You'll see from our guidance, we seek to continue that growth going into the future, and I'll share with you why. So TAVALISSE, fostamatinib, is indicated for the treatment of adult chronic ITP, immune cytopenia, from patients who had an insufficient response to a prior therapy. ITP is an autoimmune disease where the body destroys its own circulating platelets. So these patients suffer from very low platelet counts and in constant fear of bleeding. Bleeding becomes a major episode, may be requiring emergency room visits to stop it. What TAVALISSE, fostamatinib, is able to do is dampen that autoimmune destruction process, and therefore, allowing platelet numbers to rise so they can live near normal lives. So it was an important contribution to the treatment of ITP. This is, as I mentioned, a Rigel-discovered product, our first product, and we were able to launch it in 2018. And since 2018, we've grown the product substantially. This past quarter, reaching $31 million in net product sales, which is really an impressive continued growth. As you see here, 21% growth in sales over the same quarter last year and growth in bottles directly to patients in clinic. This quarter, a record quarter in terms of bottles shipped to patients and clinics and a record quarter in terms of bottles sold to the market. That includes the impact of inventory. We had some inventory increase this past quarter, which is typical of Q4s in our sector. Our second product is REZLIDHIA or olutasidenib. REZLIDHIA is indicated for the treatment of adult patients with acute or refractory AML with a susceptible IDH1 mutation. This is a product we in-licensed from Forma Therapeutics. We in-licensed -- the product had already had its NDA filed. We helped manage the NDA to approval. And then we launched the product. So it's been on the market in '23 and '24 available to patients, and really has performed very nicely for us. It's still in the -- in its launch phase. And so you see here, $7.4 million in sales this past quarter, impressive growth over a year ago, but that's to be expected because this product is still launching and still being made available to new patients. There's a fair amount of growth here for this product as we continue to position it within this market. And we're really excited about the opportunity, not only in relapsed/refractory AML, but I'll share with you in a few minutes why we think this has potential in a wide range of other hem/onc conditions and glioma, areas with significant unmet medical need. Our third product is a product named GAVRETO. GAVRETO is indicated for the treatment of RET fusion-positive non-small cell lung cancer and thyroid cancer. We acquired U.S. rights to GAVRETO this year from our colleagues at Blueprint Medicines. GAVRETO was being sold previously by Genentech and Roche in the U.S. They decided to return that product rights to Blueprint. And we were able to take on the product and keep the product on the market. So patients benefiting from GAVRETO are still able to take this product. So we've had this product probably about 6 months. Genentech had been selling about $28 million a year with this product. For Genentech, not a very impressive numbers, you may surmise. But we were delighted that in our first full quarter of the product in Q3 of this past year, we were able to achieve $7.1 million, effectively the same run rate that Genentech had been showing. And this is impressive because usually, when you transfer a product from company A to company B, there's leakage, some patients don't continue on product, sales drop. That's fairly typical for the first few quarters, then recover. Glad to say we did an excellent job with our friends at Blueprint and Genentech to be able to maintain all the patients that were taking the product and keep the sales level at about the same $7.1 million. Then what happened in Q4, you see here is that we actually had new patients and new doctors taking the product. And this is, again, impressive because it's just barely new to us, but already, we're sharing the data underlying this product with clinicians. And now our sales is $8.1 million. So we've already exceeded what Genentech had been doing in only our second quarter for this product. So we really are delighted to have this as part of our portfolio. It's a product that meets a substantial need in this area and an area where we have very solid data to share with clinicians about the use of the product. So all three of these products are products that we're incredibly happy with, and we see continued growth that I'll talk a little bit about that in terms of our guidance. Turning to the clinical development update. On this slide is how we're going to expand the portfolio. On the right is in-licensing and product acquisition. Like with GAVRETO and like with REZLIDHIA, we're looking for differentiated assets in hematology or oncology, or related areas that are late stage. By that, we mean we have registrational data in hand or the NDAs have been filed or the NDA has been approved or the product is already on the market. So effectively, we're looking for something that we'll be able to launch or in the market in the very near future. And that's important for us because we're looking for these assets to be accretive relatively shortly and contribute to the cash position of the company in the short term. We're also looking for products that are synergistic to our current sales capability and capacity. That is, we don't want to expand the sales organization greatly in order to sell the new products. We didn't have to do so with either of these two products. We added some headcount, but not very many. And as a result of that, the impact of these products on our P&L is substantial because much of that sales dropped down to the bottom line, and that's exactly what we want to achieve with future in-licensing and acquisitions. On the left side of this slide is how we're going to grow in not incremental manner but in a substantial manner with the opportunities that you see here being potential game changers and truly transformational for the company. Two things I'd like to highlight. One is our R289, Rigel's IRAK1/4 inhibitor, which we'll discuss in lower-risk MDS. And the second is olutasidenib, which we're looking at a variety of different things beyond AML. And we're looking to activate a trial in glioma this calendar year. I'll tell you a bit more about that. With fostamatinib, we're putting in place a number of investigator-sponsored trials to help elucidate other benefits of SYK inhibition in the form of fostamatinib. Let's go forward with R289, IRAK1/4 inhibitor. IRAK -- this molecule was a Rigel invented molecule. And here, I'd like to share with you the value proposition for R289 in lower-risk MDS. There are about 12,000 patients that are previously treated in lower-risk MDS in the U.S. However, despite the size of that opportunity, there is a substantial lack of effective therapies in this area. Really disappointing how little there is available that works well and works consistently. For example, HMAs are used frequently in this area. They were approved over 20 years ago. Response rate is about 20% only. So not very effective, but they're commonly used. Other agents in this area have their own issues and their own deficits, which I think presents opportunities for us. It's a large area with substantial unmet need. What's interesting about this area in addition is in the last 5 and certainly 10 years, the inflammatory component of lower-risk MDS has become much and much better appreciated as a key component of the pathogenesis of lower-risk MDS. Effectively, it's a cytokine storm in the bone marrow is what best describes low-risk MDS. And the results of that inflammation is that there is not normal hematopoiesis in the bone marrow and cells do not differentiate normally. And you have immature cells, inappropriate cells as a result cytopenias, anemias, neutropenias are very common in this disease. Our thinking is if we could address the inflammatory component of this disease, we may have a real benefit and a benefit that's very different in its approach from what's currently available. If we could block toll-like receptor signaling, TLR, and IL-1 receptor signaling, we may have a very active molecule. We have in 289 exactly that, and I'll share some information on this with you. A molecule that is very effective in blocking these two inflammatory signaling pathways. We've done a clinical study looking at this in normal healthy volunteers where we've given them approach, and I'll share the data with you and showed we're able to suppress these inflammatory cytokines very effectively. The FDA has granted us Fast Track designation about 1.5 months ago. And then last month or earlier this month, granted us orphan drug designation as well, sharing that they appreciate that there's a utility and value in moving this product forward in lower-risk MDS. And at the ASH meeting just passed, we were able to share some very promising but early data from a Phase Ib study in lower-risk MDS, I'll share that with you here as well. Here's the treatment landscape for lower-risk MDS. Again, MDS is a clonal disorder of hematopoietic stem cells, leading to dysplasia and ineffective hematopoiesis. Initial therapies are erythropoiesis-stimulating agents and transfusions. Now those are not approved, they're in a light green there, simply to highlight they're not approved agents, but they're commonly used in the non-del5 area. Del5 patients, a small percentage of the overall population has an approved agent, as you see there. Failing ESAs and transfusions, these patients typically receive the product named luspatercept. Or most recently this past year, a new product was approved, RYTELO or imetelstat, from Geron was also approved. Now these agents have about a 40% response rate in this segment, but a fair number of patients that is not working for 60% of the patients. And then after they do work, many of them do relapse and require something else. What's currently used are the HMAs, a couple of these, azacitidine, decitabine are used in the relapsed/refractory setting. The response rates are about 20%. So it tells you what a deficit of disorders of treatments that are available in this category. If you fail in HMA, there really is nothing for you. Nothing approved. You're resorting to experimental drugs, hoping something works for these patients. So really, the effect -- the lack of effective therapies in an area as large as this is really an important thing. And we happen to have a drug that may address something fundamental in this disease process and that's why we're excited about trying it. Let me tell you why we're excited about our drug. IRAK1/4 address key signaling pathways, as I said, toll-like receptor and IL-1 signaling pathways. And interestingly, you need IRAK1/4 to provide more effective suppression of these IRAK signaling. If only -- you only address IRAK4, there's compensatory mechanisms that IRAK1 allows you to still have an inflammatory environment. So you really need 1 and 4. And I'll show you why 1 and 4 is better in the cell-based assays in a second. And if you're able to do this, and you're able to do this in humans, and I'll show you the results of a human study, you're well on your way. By the way, R289 is a prodrug of R835. In the body, 835 does all the work. There's a complete conversion of 289 to 835 in the gut in a manner that's well established. Here's the cell-based assets I wanted to share with you and why an IRAK1 and 4 may be better than just an IRAK4. This is a published IRAK4 inhibitor that's well studied in the clinic. As you see here, it inhibits IRAK4 nicely, but completely inactive against IRAK1. The result of that is that you get only partial inhibition of these inflammatory cytokines. With our molecule 835, it inhibits both IRAK4 and IRAK1 about equally potently, and you do get complete inhibition of these inflammatory cytokines. Now you may ask, well, who else has an IRAK1 and 4 inhibitor? The answer is no one does. We're the only company in the clinic with an IRAK1 and 4 inhibitor. IRAK4s have been studied primarily for immune disorders, RA, psoriasis, et cetera, but really very minimal effort in the hem/onc space or low-risk MDS area. So we're the only ones that have an IRAK1 and 4. And it goes to the way we discovered the molecule using a cell-based functional screen rather than a biochemical assay that others have used. So we're delighted to have this molecule because it is unique and we think it's well suited to this indication. We took this molecule and we put it into its first human study. Now this is a study in healthy volunteers. What you do is you give them an LPS challenge. LPS is a protein that causes a cytokine storm in the bodies of these patients -- these volunteers. Now this is done in a hospital setting, so there -- everything is very safe. And then you test whether your drug at different doses is able to reduce that inflammatory cascade. The answer, as you see here, it's able to do so quite dramatically. Reducing TNF, IL-6, IL-8, many other inflammatory cytokines dramatically. Now this is an artificial condition. You created an insult, you solved the insult. We knew when the insult was there. But if we are able to do this chronically, if we're able to give this drug on a long-term basis and reduce the inflammatory cytokines in a person who's suffering from that, say, someone with low-risk MDS. We may have a unique approach to treating low-risk MDS that is fundamental to that disease process. And that is what we've begun to do with this trial. This is Slide 20 now. R289 is a Phase Ib -- is in a Phase Ib study in relapsed/refractory AML -- lower-risk MDS. And we started a dose escalation study here beginning at dose level 1, frankly, too lower dose, but the FDA asked us to do that. Then 500 QD level 2; 750 QD, level 3; dose level 4, 250 BID. And then currently, we're enrolling dose level 5. We may enroll dose level 6 at 500 BID as well. We haven't finalized that decision. At the ASH meeting, we presented data from dose level 1 through 4. What we're looking for is safety AEs and then secondary endpoints being transfusion independent. Most of these patients are transfusion dependent. And our goal is to get them to transfusion independence or have a hematologic improvement, that is a reduction in transfusions. That's meaningful. Not surprisingly, we enrolled a very heavily pretreated population. About 77% had luspatercept in the past, 73% had HMAs in the past, a median prior therapy of 3. Mainly older people, that's who have lower-risk MDS and importantly, mostly high transfusion burden patients, as you see there, 73% had greater than 8 RBC units in the prior 16 weeks. So a patient population that's very challenging and very difficult to treat that have failed almost everything available to them. The safety was well tolerated, low incidence of cytopenias and infections. You see here on this slide, the 500 QD dose group, really just a minor things here in diarrhea, a bit more things in the 750 QD dose group with increases in ALT and AST being perhaps a little bit more prominent. Really no issues with the 250 BID simply because exposures were not at the high enough levels there. I'll show you that. So 250 QD, fairly low exposure. So not surprising that we didn't see much there. 500 QD, we did see higher exposures and not surprisingly, we saw some responses. I'll show you that in a minute. At 750 QD, also higher exposures and also some responses. At 250 BID, not very high exposures and not surprisingly as yet, no responses. And here's the data. As I mentioned, 250 QD was too lower dose and we kind of knew that going in. We did 3 patients, none of them responded, not surprisingly, given the low exposures. At 500, though, we saw 2 responders. And here they're marked in little red stars and red diamonds. And what you see is that 2 of them responded. One actually really very nicely. So we have 2 of 5 evaluable transfusion-dependent patients, showing a response or a 40% response rate. Patient 9 on this chart was not transfusion dependent. So you really can't count that person. You can't get someone who's not transfusion dependent to transfusion independent. So 2 of 5 transfusion -- evaluable transfusion-dependent patients show the benefit. In the 750 dose group, something similar. You see 2 patients there, patient 10 and 11, showing a responses. Again, 2 of 5 transfusion-dependent evaluable patient. One patient 15 dropped out very early, so it was not an evaluable patient. So we're very happy that this is the initial result. We've shared this with clinicians involved in the study, and they were really impressed with this data because it's remarkable that anything works with these patients. And given the high failure rate of other drugs, it's pretty impressive that we were able to achieve this. I'm going to show you this chart, this is the 4 responders we had in those 2 dose groups. And I'm sharing this with you to highlight that all of them were high transfusion burden. One was a lower transfusion burden patient. Many therapies failed. ESAs, experimental medicine, experimental medicine HMA in patient 5, ESA, HMA, luspatercept, curiously fostamatinib, experimental medicine in this indication in an anti-TIM antibody. So quite a number of things that they failed, yet we were able to get them to a response. And that's really remarkable given this patient population. It gave us considerable confidence and excitement about going forward. Here's the hemoglobin levels in these transfusion independent patients 3 of them. And you see the hemoglobin levels responded quite nicely, as you expect to see consistent with the results that we showed in terms of transfusion independent. But even the patients that were not responders in green here, also saw increases in their hemoglobin levels as well. So there's clearly a benefit that is even beyond transfusion independent to these patients but impressive results consistent with the earlier data shared with you. So in summary, the incidence of grade 3/4 cytopenias was low and infections was low. In patients that had 500 QD and 750 QD, they were able -- which is higher exposures, we were able to show a benefit. About 40% of evaluable transfusion-dependent patients in those two segments showed a benefit. And some including a durable responses, 24 weeks in a couple of these and looking for more. There's still -- some of them are still ongoing. And patients achieving transfusion independence saw increases in their hemoglobin somewhere between 2.3 to 5.6 grams per deciliter versus their baseline. So very nice improvement in the hemoglobin levels as well. So what's coming next for this program? In 2025, we're going to finish the dose escalation phase. We're going to initiate dosing of the expansion phase that is we're going to choose 2 doses, maybe 1 or 2 and then go into an expansion phase. We're going to discuss with FDA what the registrational path is, and we're going to present this data and discuss the registrational path in a medical meeting sometime later this year. So it's pretty exciting to have a drug like this with a major -- an area that's large, that has tremendous medical need and may offer a completely new approach to treating this indication. The early data seems really exciting to us and to clinicians involved. Let me move to olutasidenib and I'll rush through this a little bit to give some time for questions. Our IDH1 inhibitor. So what we're doing here in glioma is that you may know, glioma is an area that is incredibly challenging. An area where there has not been until recent much improvement in this area. Patients with gliomas suffer greatly. And one thing you may not know is that IDH mutations are common in grade 2 and 3 glioma about 70%. This past year, last 1.5 years, IDH has been more and more appreciated as a potential approach to treating these patients with IDH mutations. Vorasidenib, a molecule from Servier, originated from Agios, was approved in grade 2 low-grade gliomas, which underscores that there's potential for IDH inhibitors here. Our molecule, olutasidenib, was part of a Phase II -- I/II trial that our colleagues at Forma did. About 26 patients in this study, and there's a publication in Neuro-Oncology. And what it shows in the highly treatment refractory patients, really patients that have failed everything and still had disease. We had 2 patients that achieved partial responses, both in enhancing tumors where it's harder to treat and 10 of these patients achieved stable disease, which in this category and given that patient population is a really good result. So we were delighted with that. We put in place last year a collaboration with the CONNECT organization. They are doing a TarGeT-D study, which will investigate oluta as part of that umbrella study in high -- in maintenance therapy for high-grade gliomas. This is a study we put in place. They're getting up and running. In a matter of weeks, the CONNECT study will launch and we should have data sometime in the future, but we're delighted to have that collaboration in place and delighted to have them work in the maintenance facet of this. Ourselves, we'd like to announce that we're going to start a Phase II clinical study in this year in recurrent glioma. And we'll come back to you with more details about that study in the near future, but we're excited about the opportunity. It's a major opportunity, an area with, again, significant unmet need, when we have a molecule, this IDH inhibitor that has been shown to be beneficial and the whole class of IDH has been shown to be an area where there's opportunity to really contribute substantially to the treatment of gliomas. And I can't tell you how exciting we would be to say we have a drug that treats brain cancer, after so much disappointment and lack of therapies available for these patients. So we're super excited about this. As our colleagues in -- at the CONNECT organization, as I mentioned, the lower bullet point, it's a Phase II study in patients that are newly diagnosed, that will treat them with oluta and TMZ, a commonly used agent in this area for a year, and then switch to oluta monotherapy for the second year. It's a study we're sponsoring and we're delighted to do so. We're looking forward to this initiation of enrollment and then data generation in addition to our own study. Let me move on to a strategic alliance we put together with MD Anderson. You may know MD Anderson is one of the premier cancer centers in the world. They pride themselves and rightly so are creating the new standard of care in various cancers. And we talked to them about oluta. They were delighted with the data we shared with them. They shared with us the belief that this could be an excellent contributor to the treatment of various cancers, blood cancers. And we and they are going to work closely together to explore this. So we put in place a collaboration that will be a 4 clinical trial collaboration. First, in AML, where we're looking initially in relapsed/refractory AML patients, and then newly -- and newly diagnosed patients. And that segment is important because it will generate important data in newly diagnosed AML. That trial that checkmark means it's activated. In the short time, we'll activate another trial in higher-risk MDS as well as MPN. And we've already activated monotherapy trial looking at CCUS, which is a precursor to lower-risk MDS and lower-risk MDS. And in addition, we've activated a trial in post-transplant maintenance for IDH-mutated malignancies. So 4 trials, 3 of them already activated in key areas to generate important data for oluta in areas related to AML and surrounding areas. So we're excited about this collaboration. We're excited that it's going to generate data for us to share with you in the upcoming years. MD Anderson is excited about this themselves. They have a large patient population, so they can enroll some of this nicely for us and help us present the information here. So delighted by this and delighted that now we have activations going on. Let me just touch for a minute on our RIP kinase inhibitor. RIP kinase is also an immune target. We had this program at Rigel. We had discovered a number of molecules, including R552. We partnered this program broadly with Lilly. There are two facets to it. One is the immune disease, where the lead molecule R552, now called ocadusertib is in Phase IIa study in rheumatoid arthritis. So they're enrolling this study, and we will in the near future have interim data on this trial. The second part is a CNS disease, where they're looking at RIP inhibitors that cross the BBB. We've given them a basket of these inhibitors that do so. And Lilly is now working on selecting which one they want to move into the clinic and then we'll conduct preclinical work to allow that to happen. It's an area with tremendous opportunity for TNF signaling blockade, but in addition, really pro-inflammatory necroptosis is the one area where this one really highlights the benefit of RIP kinase inhibition. And Lilly has a strong interest in rheumatoid arthritis in other areas in immunology and obviously, in CNS diseases. So really an ideal partner for us to work with in moving this program forward across both of those different areas. Let me go to financials. This is a slide I'm very proud of. It shows you here our quarterly results for each of the -- for the total of the products. As you see, coming out of COVID, we were selling about $16 million of TAVALISSE sales. That's in the orange bars. This past quarter, we reported $31 million, almost a doubling of those sales. And that's a very nice and steady growth for TAVALISSE, and we look for that to continue. In addition, we in-licensed REZLIDHIA, got it approved, got it launched. And you see in launch phase, it was there. And then now it's beginning to make some meaningful contributions, $4.9 million, $5.2 million, $5.5 million, $7.4 million in product sales for REZLIDHIA, a nice contribution. And then the acquisition of GAVRETO has already -- as I mentioned earlier, $7.1 million last quarter, $8.1 million this quarter. So the sales are increasing nicely, in part driven by continued performance from TAVALISSE, but then meaningful contributions from these two in-license acquired products. They are now about 1/3 of our business and probably will continue to grow in that percentage. As I mentioned, our cash position improved by about $20 million in the calendar year '24 from the start to the end there. And for the first time, we've given guidance, and I think this is important because we're confident in where this business is going. What we guided towards is total product -- total revenue of $200 million to $210 million, and that's comprised of net product sales of $185 to $192. Remind you, 2024 product sales were $145 million. So that's a $40 million increase in product sales in this upcoming calendar year. And we're comfortable we can achieve that given what we know about these products and their stage in launch and their stage in being part of Rigel's portfolio. It's about a 30% increase at the midpoint there. And I think that's a good guidance. It's good growth in these products. We're also projecting contract revenues outside -- and this is from our partners outside of the U.S., who sell TAVALISSE in Europe and Asia primarily of $15 million to $18 million. So in addition to that, financial discipline. We anticipate being net income positive for the calendar year '25. We haven't said how -- to what degree because we want to use these funds to fund existing clinical programs and the new clinical programs I discussed with you today. So we're able to take those exciting opportunities with 289 in lower-risk MDS, oluta in glioma and other areas and fully fund them ourselves from our own cash flows. That's an exciting place to be as a company. And I think that's a truly transformational result that we've been able to achieve this at this stage of our company and given the environment that we're in. So we're delighted by this and delighted, obviously, to talk more about this and give you updates as the year progresses. What we're doing in '25 is continue to grow the products, TAVALISSE, REZLIDHIA and GAVRETO and strong year-over-year growth. Like I said, the midpoint of that guidance is about 30%. We're going to couple that with continued financial discipline, allowing us to fund the -- and advance the development programs we discussed and continue to look at other in-licenses and acquisitions to meaningfully add to our near-term cash flow. So with that, I'd like to thank you, and I think we have about 4 minutes for questions.

If anybody in the audience has a question, just raise your hand and we'll have a mic runner get you a microphone. But Raul, thank you so much for being here today. Really impressive everything that you're doing, both on the commercial and clinical side. Maybe just to start with the commercial business, you reported strong Q4 revenue. At a high level, could you just talk us through how you're thinking about Q4 and then 2024 as a whole?

Yes. So 2024 was a really a banner year for us. We achieved growth in all the products. Most -- every quarter was a record quarter for each of the products, which is fantastic and cumulative, I think, a really stellar year for us. The new products are contributing very nicely, both GAVRETO and REZLIDHIA. But not to be left behind, TAVALISSE is growing very nicely as well. And in part, it's due to doctors becoming familiar with the product, using it across different types of patients. And now that they've used it once they had success, they're far more likely to use it again and again. And that simply takes some time, to be honest with you. And it's been like 6 years on the market now. But that's what's required for them to get comfortable using something new. And once they use it, they use it again and again, which presents barriers to entry to other succeeding products.

Awesome. Maybe turning over to R289. So you detailed the data presented for R289. But maybe just at a higher level, like what gets you excited about this data and why do you think it's promising?