RIGL - NASDAQ

Greetings, and welcome to Rigel Pharmaceuticals' financial conference call for the fourth quarter and full year 2024. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce our first speaker, Raymond Furey, Rigel's Executive Vice President, General Counsel, and Corporate Secretary. Thank you, Mr. Furey. You may begin.

Welcome to our fourth quarter and full year 2024 financial results and business update conference call. The financial press release for the fourth quarter and full year 2024 was issued a short while ago and can be viewed along with the slides for this presentation in the news and events section of our investor relations site on rigel.com. As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 2024, on file with the SEC. Any forward-looking statements are made as of today's date only, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I'd like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez.

Thank you, Raymond. And thank you, everyone, for joining today. Also with me today are Dave Santos, our Chief Commercial Officer, Lisa Rojkjaer, our Chief Medical Officer, and Dean Schorno, our Chief Financial Officer. Beginning on slide four, we will provide an overview of Rigel Pharmaceuticals' business and our numerous accomplishments in 2024. For those that are new to the company, let me take a moment to review Rigel's overall corporate strategy to grow our hematology and oncology business. Our strategy is focused on three main goals: first, expanding our commercial portfolio and increasing product sales; second, advancing and growing our pipeline through internal development and strategic collaborations; and third, maintaining financial discipline. 2024 was a transformational year for Rigel Pharmaceuticals as we delivered on all three of these goals. I will take you through each of these accomplishments in more detail. In 2024, we set another record year of sales. As a result of our effective commercial execution, we reached our highest commercial portfolio sales ever, at $145 million, a 39% growth over 2023. This significant revenue growth was driven by the strength of TAVALISSE and Rezlidia sales and the addition of Gavreto, our third product, and our second in-licensed product, which contributed $17.1 million in net product sales since we added it to our portfolio in June. We also generated revenues from our partners where TAVALISSE is commercially available, and our partners continue to make progress towards expanding TAVALISSE access to other geographies. Recently, Knight and Kissei announced regulatory approvals for TAVALISSE in two new countries, Mexico and the Republic of Korea, respectively. Once commercially launched, ITP patients in these countries can also benefit from TAVALISSE. For Rezlidia, we actively pursued new collaborations and executed new license agreements with our partner, Kissei, in three countries in Asia, and with Dr. Reddy's for numerous territories outside of the US. Also in 2024, on our second goal, we made significant progress in our development pipeline. We continue to evaluate R289, our dual IRAK1 and 4 inhibitor, in an ongoing Phase 1b study in patients with lower-risk MDS. We presented encouraging initial safety and efficacy data from that study at the ASH Annual Meeting in December. Enrollment in the dose escalation portion of the trial, where we recently completed the fifth dose level, and have now opened for enrollment a new sixth dose level at 500 milligrams BID. For olutasidenib, our strategic collaborations with MD Anderson and the Connect organization continue to progress. These trials provide us with the opportunity to explore olutasidenib in a range of IDH1 mutant cancers in a time and cost-efficient manner. We're excited to report that all four studies from our multi-year strategic development alliance with MD Anderson have now opened for enrollment, and the Phase 2 study of olutasidenib in high-grade glioma in collaboration with Connect has also recently opened for enrollment. Lisa will provide you an update on these development programs in a few minutes. And lastly, in 2024, on our third goal, maintaining financial discipline. By maintaining financial discipline, we were able to, for the first time, generate full-year net income of $17 million, and our cash balance increased by more than $20 million for the year. These accomplishments enable Rigel Pharmaceuticals to continue to successfully implement our strategy. Moving on to the next slide, we have continued to grow our net product sales over time, with a compound annual growth rate of 32% from between 2021 and 2024. TAVALISSE grew nicely over that period, and the addition of Rezlidia in late 2022 and Gavreto in 2024 has provided additional contributions to that growth. All three of these products achieved new highs in 2024. And in 2025, as you can see on slide six, we're expecting approximately $145 million to $192 million in net product sales for the year, approximately a 28% to 32% growth compared to 2024. So just to summarize, 2024 was a transformational year. We continue to grow our hematology and oncology business while at the same time becoming a profitable company. And with that, I'll turn the call over to Dave to provide a commercial update. Dave?

Thank you, Raul. On slide eight, you'll see our three commercial products: TAVALISSE, Rezlidia, and Gavreto. We are very pleased with the strong growth in revenues in the fourth quarter and full year 2024. Moving to slide nine, you see how our quarterly and annual sales have evolved since 2021. We've grown each quarter's sales over the previous year, and that growth continues, particularly from last year to this year. We started the first quarter of 2023 with $23.8 million and are now reporting $46.5 million for the fourth quarter of 2024. That growth has been driven by our strong commercial execution and consistently building quarterly demand for TAVALISSE and driving broader awareness of Rezlidia through the first two years of its launch. In addition, our ability to successfully and seamlessly transition Gavreto into our portfolio has significantly expanded our top line. We compared to the fourth quarter of 2023, we generated 58% growth in the fourth quarter of 2024. For the full year 2024, we delivered record revenues of nearly $145 million, an increase of $41 million or 39% compared to 2023 net sales of $104 million. Our commercial team has been dedicated to execution, driving continued momentum for TAVALISSE and improving both institutional and community demand for Rezlidia, and successfully transitioning Gavreto patients and accounts to Rigel Pharmaceuticals' product. My sincere thanks to the entire team for all their hard work to grow our business in 2024. Slide ten shows a summary of our commercial performance by product. First on top of the list, I'm pleased to report another strong quarter in which we generated $31 million in net product sales, an increase of 21% compared to the fourth quarter of 2023. This growth was driven by strong patient demand, with another consecutive quarterly record high. We continue to grow TAVALISSE demand through both refills from patients who stay on the product and new prescriptions for patients who are starting TAVALISSE for the first time. Moving to Rezlidia, we reported $7.4 million in net product sales, almost doubling revenue from the prior year period as we focus on improving Rezlidia adoption both in institutions and the community by raising awareness of Rezlidia's efficacy, particularly in patients who have failed upfront therapy with venetoclax. And lastly, for Gavreto, in our second full quarter selling the product, we delivered $8.1 million in net product sales in Q4. We are very happy with the success in transitioning over Gavreto patients, prescribers, and accounts to Rigel Pharmaceuticals' distribution network. Importantly, our $8.1 million of net product sales in the fourth quarter represent a run rate above the $28 million in annual sales of Gavreto in 2023 under prior ownership. We are especially pleased with Gavreto's upward trajectory during last year's transition and are now focused on building on that momentum in 2025. Moving to slide eleven, we hit several meaningful milestones with our portfolio in 2024. Importantly for TAVALISSE, 2024 was the first year to achieve more than $100 million in net sales. It continues to grow steadily as the foundation of our portfolio, consistently hitting new record quarterly highs in bottles shipped to patients and clinics. That steady growth has been driven by more new patients starting on TAVALISSE each quarter and the subsequent increased carryover that's generated. In 2025, we expect that trend to continue. For Rezlidia, we more than doubled both bottles shipped to patients and clinics as well as net sales in 2024, and we believe we still have significant opportunity to grow Rezlidia's use in mutant IDH1 relapse refractory acute myeloid leukemia. We continue to find that as clinicians become more aware of Rezlidia's efficacy in post-venetoclax patients, they believe it's clinically meaningful as these patients are very difficult to treat with other therapies. We believe we can build on the scientific data currently available in this important population of AML patients and continue to grow Rezlidia's use in 2025. Lastly, in 2024, our successful transition of Gavreto demonstrates our nimble and highly adaptable organizational capabilities. We've fully leveraged our commercial and medical affairs infrastructure and expertise to meaningfully expand our hematology and oncology portfolio and quickly generated $17.1 million of incremental net sales in 2024. The Q4 Gavreto net sales result of $8.1 million reinforces how smoothly and effectively both new and existing patients were transitioned. Furthermore, the fact that we were also able to significantly grow TAVALISSE and Rezlidia while that transition was ongoing is a testament to our organizational capabilities and operational efficiency. In 2025, we can continue to grow Gavreto, particularly since the use of RET inhibitors in non-small cell lung cancer should continue to expand in the frontline setting. New non-small cell lung cancer treatment guidelines released by the National Comprehensive Cancer Network, or NCCN, in January now recommend that if a RET inhibitor was not used in the frontline setting, clinicians may switch frontline therapy to a RET inhibitor once the RET fusion is confirmed. We believe that RET inhibitor use will expand in non-small cell lung cancer in 2025 and beyond, and Gavreto will grow in turn. Finally, moving to slide twelve, we're incredibly excited about our work to expand access to our patients in markets outside of the US. TAVALISSE is commercially available in Japan, Europe under the brand name Tavlesse, and in Canada and Israel via our partners Kissei, Grifols, and Medison, and that's generating sustainable revenues each quarter. In addition, our partners continue to pursue regulatory approvals for TAVALISSE in new markets. As Raul mentioned, Knight Therapeutics announced it has received regulatory approval for TAVALISSE in Mexico, and recently, Kissei announced regulatory approval for TAVALISSE in Korea. In 2024, we also looked to find partners to develop and commercialize Rezlidia in ex-US markets. We expanded our relationship with Kissei to include Japan, Korea, and Taiwan for Rezlidia in all potential indications. And in late 2024, we entered into an exclusive license agreement with Dr. Reddy's for Rezlidia in all potential indications throughout Dr. Reddy's territory, which includes Latin America and other territories. We are pleased that access to our products is expanding outside the US, and we continue to explore other opportunities for partnerships outside the US to bring our products to other markets and patients around the globe. I will now pass the call over to Lisa to provide an update on our development pipeline. Lisa?

Thanks, Dave. We made meaningful progress in 2024 and look forward to continued execution on our strategy to expand our hematology oncology portfolio in 2025. I'm on slide fourteen. First, from our development pipeline, R289 is our novel dual IRAK1 and 4 inhibitor that is currently being evaluated in the Phase 1b study in patients with relapsed refractory lower-risk myelodysplastic syndrome, or MDS. We're excited that R289 has been granted both fast track designation for the treatment of patients with previously treated transfusion-dependent lower-risk MDS and orphan drug designation for MDS by the FDA. Furthermore, as part of our Rigel-sponsored development programs and alongside our partners, MD Anderson and the Connect Cancer Consortium, olutasidenib is being evaluated in new indications. We believe olutasidenib has potential in several cancers where mutated IDH1 plays a role, such as glioma, additional AML segments, and MDS, either as monotherapy or in combination. We expect to initiate a Rigel-sponsored Phase 2 study to evaluate olutasidenib. In addition, as Raul mentioned, all four clinical trials under our MD Anderson collaboration are now open for enrollment, as is the Connect study focused on high-grade glioma. We also remain focused on evaluating potential opportunities to in-license or acquire products that would be a strategic fit for our portfolio. We're looking for differentiated products in hematology, oncology, or related areas. Products that are late-stage, possibly with registrational data, soon to have registrational data, or more advanced, and products that can leverage our hematology and oncology infrastructure. As demonstrated with our acquisitions of olutasidenib and pralsetinib, our goal is to continue to find assets that align with our organization, pipeline, and ability to execute. Now we'll spend a few moments discussing the updates from our R289 program. To help frame the discussion, slide sixteen presents an overview of the value proposition of R289 in lower-risk MDS. There are about twelve thousand previously treated lower-risk MDS patients in the US. Recent development efforts in lower-risk MDS have focused primarily on first-line therapies. However, there's a high unmet need for next-line therapies, particularly for previously treated transfusion-dependent patients. Dysregulation of inflammatory signaling is key to the pathogenesis of lower-risk MDS, and IRAK1 and 4 mediate this process. Blocking both IRAK1 and 4 may suppress marrow inflammation and leukemic stem and progenitor cell function and restore hematopoiesis. R835, the active moiety of R289, blocks Toll-like receptor and IL-1 receptor signaling in vitro and was active in various preclinical models of inflammation. Clinical proof of concept of this anti-inflammatory effect came from a healthy volunteer study in which R835 markedly suppressed LPS-induced cytokine release compared to placebo. As a reminder, R289, which is currently being evaluated in the clinic, is the oral prodrug that is rapidly converted to R835 in the gut. R289 has both FDA fast track and orphan drug designations, giving the molecule an expedited regulatory pathway, potential priority review, and seven years of market exclusivity upon approval. Both of these designations underscore the agency's interest in this rare disease and their willingness to collaborate with Rigel Pharmaceuticals in the development of R289. In addition, R289 has thus far demonstrated a promising preliminary clinical profile in a Phase 1b study. Initial dose escalation data that were recently presented at the ASH Annual Meeting will be reviewed on today's call. On slide seventeen, you see the treatment landscape for lower-risk MDS. MDS is a clonal disorder of hematopoietic stem cells leading to dysplasia and ineffective hematopoiesis. The main consequences for patients are anemia and transfusion dependence, which adversely impact their quality of life. In addition, infections, iron overload, and aside from transfusions, initial therapies include erythropoiesis-stimulating agents, or ESAs, if patients are eligible, and luspatercept. A metal stat was approved earlier this year for ESA failure, high transfusion burden, lower-risk MDS. With eight-week transfusion independence rates approaching 40% with luspatercept and omidalstat, many patients require an alternative treatment option. Although hypomethylating agents, or HMAs, are approved, the percentage of patients achieving transfusion independence is low. Therefore, there is a high unmet need for safe, effective treatment options following failure of approved therapies, particularly for previously treated transfusion-dependent patients. On slide eighteen, you'll see the design of our ongoing open-label dose escalation dose expansion Phase 1b study in relapsed refractory lower-risk MDS patients with either symptomatic anemia or transfusion dependence. The study was recently updated to include a sixth dose level, 500 milligrams BID, and to facilitate the randomized comparison of two dose levels and expansion to optimize selection of the recommended Phase 2 dose. The primary endpoints are safety and selection of the recommended dose for expansion. Secondary endpoints include transfusion independence, hematologic improvement, response rates, and PK. The study continues to progress well with the sixth dose level, 500 milligrams BID, open for enrollment. Once the recommended Phase 2 dose has been determined, an exploratory cohort of first-line lower-risk MDS patients will be open to evaluate R289 in an earlier line of therapy. Now I'd like to walk you through the initial dose escalation data that were presented at the ASH Annual Meeting. On slide nineteen, we start with patient characteristics. Data on twenty-two patients were reported using an October 25, 2024, data cutoff date. The median age was seventy-six, and about sixty percent of the patients were aged seventy-five or above. The median number of prior therapies was three, ranging from one up to eight, and more than seventy percent of patients had received an HMA or luspatercept. The majority of patients, seventy-three percent, were high transfusion burden at baseline. The median time on therapy was four point six months. In summary, these were elderly, heavily pretreated patients with a high transfusion burden at baseline. Moving to slide twenty, we'll review the safety findings. R289 was generally well tolerated. The most common treatment-emergent adverse events in twenty percent or more patients, which are not shown on the slide, were diarrhea and fatigue, followed by chills, nausea, and pruritus, all of which were grade one or two. The most frequent grade three or four adverse events were two events each of anemia, platelet count decreased, pneumonia, and alanine aminotransferase, or ALT, increased. The treatment-related adverse events are shown on the slide. Importantly, for this patient population, the incidence of grade three or four cytopenias and infections was low. There was one dose-limiting toxicity reported, a grade three or four transaminase increase in one patient at the seven hundred and fifty milligram daily dose level. Serious adverse events occurring in two or more patients were pneumonia and upper GI bleed. Both occurred in two patients each and were unrelated to therapy. On slide twenty-one, we show the preliminary efficacy data. The swimmer plot shows each patient and the red cell transfusion by dose group, starting with the lowest dose group, two hundred and fifty milligrams daily on top. Per the IWG 2018 criteria, the transfusion history for each patient was collected for sixteen weeks prior to R289 administration to establish the baseline transfusion frequency shown to the left of day zero, indicated by the red arrow. Two patients, numbers nine and nineteen, were not transfusion-dependent at baseline. Eighteen patients were evaluable for efficacy, meaning that they had one or more R289 doses and at least one assessment. Red blood cell transfusion independence lasting eight weeks or longer was achieved by three patients, one receiving five hundred milligrams daily, and two receiving seven hundred and fifty milligrams daily. In two patients, RBC transfusion independence lasted for more than six months, and one patient also achieved a marrow complete response. The median duration of transfusion independence was twenty-nine weeks. One high transfusion burden patient receiving five hundred milligrams daily achieved a minor HI-E response with a sixty-four percent reduction in red blood cell transfusions compared to baseline. Regarding PK, at doses at or higher than five hundred milligrams once daily, R835 plasma concentrations reached or exceeded those associated with fifty percent or ninety percent LPS-induced cytokine inhibition that was previously observed in healthy volunteers. We thought it was interesting that at these doses, hematologic responses occurred in four out of ten, or forty percent, of the evaluable transfusion-dependent patients. On slide twenty-two, we see a summary of the responding patients. The majority were high transfusion burden at baseline and had received a variety of prior therapies, including luspatercept, hypomethylating agents, and some experimental therapies. The two patients with durable transfusion independence lasting more than six months, patients four and ten, were both high transfusion burden at baseline and had received HMAs. Beneath the table are the hemoglobin levels over time for the three patients that had achieved transfusion independence. Peak hemoglobin increases ranging from two point three to five point six grams per deciliter compared to baseline were observed, indicating that R289 has the potential to correct anemia, providing support for its evaluation earlier in treatment. In summary, the initial data is encouraging, showing R289 is generally well tolerated with promising signs of efficacy in heavily pretreated transfusion-dependent patients. Now we'll shift focus to olutasidenib, our IDH1 inhibitor. Beginning on slide twenty-four, glioma is an area that is incredibly challenging where there has not been much advancement in therapeutic options. Diffuse gliomas are the most common primary brain tumor in adults, affecting approximately twenty thousand in the US each year. IDH1 mutations occur in about seventy percent of patients with grade two and three glioma and are found in up to almost forty percent of younger patients. Unfortunately, most disease recurs, and there's no standard of care therapy for relapsed patients. The recent approval of vorasidenib, an IDH1 and 2 inhibitor, in grades and grade two gliomas, has highlighted the potential for IDH inhibitors. Olutasidenib was previously evaluated in a Phase 1b/2 study in twenty-six patients, which was published in the journal Neuro-Oncology. Two patients with high-grade glioma achieved partial responses. Both had enhancing tumors, and ten patients achieved stable disease, for a disease control rate of forty-eight percent. This clinical proof of concept supports further evaluation of olutasidenib in glioma. Moving to slide twenty-five, last year, we entered a collaboration with the global neuro-oncology consortium, Connect. In Connect's target trial, a molecularly guided Phase 2 umbrella clinical trial for high-grade glioma, the Rigel-sponsored arm of the study, Target D, evaluates a post-radiotherapy maintenance regimen of olutasidenib in combination with temozolomide, followed by olutasidenib monotherapy in newly diagnosed patients between twelve and thirty-nine years of age with IDH1 mutation-positive high-grade glioma. This study was recently opened for enrollment. In addition, we recently announced that this year we plan to initiate a Phase 2 clinical study in recurrent glioma. We look forward to providing more details about that study later this year. We think this is an important opportunity as there is a significant unmet medical need in this patient population. We, along with Connect, are excited about olutasidenib's potential to provide a much-needed new treatment option to this underserved patient population, and we look forward to the data generation from the Connect study in addition to our planned study in recurrent glioma. On slide twenty-six, you'll see another important collaboration, our strategic alliance with the MD Anderson Cancer Center to advance olutasidenib more broadly into AML, MDS, and beyond. We're pleased to report that the four studies indicated in this collaboration are now open for enrollment. Turning to our partnered program, on slide twenty-eight, our RIPK1 inhibitor programs are progressing well with our partner Lilly. RIPK1 is implicated in a broad range of inflammatory cellular processes and plays a key role in tumor necrosis factor signaling. Ocaducirtib, our non-CNS penetrant RIPK1 inhibitor, previously referred to as R552, is currently being studied in an adaptive Phase 2a/2b clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis. Phase 2a enrollment of approximately 100 patients is advancing well, with preliminary analysis of the results anticipated within the first half of 2025. Our preclinical CNS RIPK1 inhibitor program is also progressing toward lead candidate nomination. In closing, as you see on slide twenty-nine, there are several upcoming milestones for our development programs in 2025. For our R289 program in lower-risk MDS, we expect to complete the dose escalation portion of the Phase 1b study. The new sixth dose level, 500 milligrams twice daily, is actively enrolling. We then plan to initiate the dose expansion phase later this year. Also, during the year, we plan to seek health authority input on the registrational path for R289, and we're anticipating presenting the dose escalation data from the Phase 1b study in the second half of the year. Then for olutasidenib, we plan to initiate a Phase 2 clinical study in recurrent glioma by year-end and also plan to provide you with more details about that study later this year. In addition, we'll continue to support the four MD Anderson studies and the Connect study. We're excited about the progress we've made in 2024 to advance these programs and look forward to providing further updates on these planned milestones in 2025. Now I'll pass the call to Dean to discuss our financial results for the quarter.

Thank you, Lisa. I'm on slide number thirty-one. We reported net product sales of $46.5 million for the fourth quarter, a growth of 58% year over year, including TAVALISSE net product sales of $31 million, a growth of 21% year over year, Rezlidia net product sales of $7.4 million, a growth of 92% year over year, and Gavreto net product sales of $8.1 million in the fourth quarter. As a reminder, Gavreto became available for sale in June of 2024. Our net product sales from TAVALISSE, Rezlidia, and Gavreto are recorded net of estimated discounts, chargebacks, rebates, returns, copay assistance, and other allowances of $19.7 million. For the fourth quarter of 2024, our gross-to-net adjustment for TAVALISSE, Rezlidia, and Gavreto was approximately 33%, 21%, and 23% of gross product sales, respectively. Our fourth-quarter revenues reflect strong patient demand and were aided by a year-end increase in inventory in our distribution channels, as we've seen in the past. As we've also seen in the past, we expect to experience a drawdown in these inventory levels in our distribution channels in the first quarter of 2025. Incrementally, we highlighted in the fourth quarter, we made certain changes to adjust that would result in continued high-quality access while reducing our distribution costs and favorably impacting our gross-to-net adjustment in the future. While this change is not expected to impact our bottles shipped to patients and clinics, we expect to experience a reduction in bottles remaining in our distribution channel of approximately 350 bottles during the first quarter of 2025. We expect the effect of these distribution channels to have normalized by the end of Q1. We also reported $11.1 million in contract revenues from our collaborations for the fourth quarter, primarily driven by Grifols and Kissei, along with $4 million in revenue from Dr. Reddy's related to the upfront fee from sublicensing olutasidenib. Under the next slide and moving down the income statement to cost and expenses, our cost of product sales was approximately $5.8 million for the fourth quarter of 2024. Total cost and expenses were $40.9 million compared to $33.8 million for the same period of 2023. The increase in cost and expenses is mainly due to higher R&D costs driven by the timing of our clinical activities, increased personnel-related costs, and increased commercial-related activities. In addition, the cost of product sales increased, driven primarily by increased product sales, higher royalties, higher amortization of intangible assets, and sublicensing revenue fees. For the full year, the cost of product sales was approximately $18.6 million. Total cost and expenses were $155.1 million compared to $137.4 million for the full year of 2023. The increase in cost and expenses was mainly due to higher cost of product sales, driven primarily by increased product sales, higher royalties, higher amortization of intangible assets, and sublicensing revenue fees. In addition, there were increases in personnel-related costs, stock-based compensation expense, and commercial-related expenses. These increases were partially offset by decreased R&D costs due to the timing of clinical trial activities related to R289, our dual IRAK1/4 inhibitor program, as well as reduced trial activities related to completed Phase 3 clinical trials during 2023. We reported net income of $14.3 million for the fourth quarter, compared to $700,000 in the same period in 2023. For the full year, we reported net income of $17.5 million compared to a net loss of $25.1 million for 2023. We ended the quarter with cash, cash equivalents, and short-term investments of $77.3 million, up from $56.9 million as of the end of 2023. Turning to our financial outlook for 2025, we expect total revenue in the range of approximately $200 to $210 million, comprised of approximately $185 to $192 million in net product sales and $15 to $18 million of contract revenues from collaborations. We also anticipate reporting positive net income for the full year while funding existing and new clinical development programs. To wrap up my section, 2024 was a tremendous year of revenue growth and continued financial discipline for Rigel Pharmaceuticals, and we look to continue into 2025 and beyond. With that, I'd like to turn the call back over to Raul.

Thank you, Dean. Moving on to slide thirty-three. As I've stated on this call, 2024 was a year of significant achievements. We reached profitability and cash flow breakeven while delivering on our corporate strategy to grow our hematology and oncology business. Going forward into 2025, our priorities are clear: continue to grow our commercial business, advance our development programs, identify new pipeline opportunities, and continue to maintain financial discipline. We anticipate growing our net product sales by approximately 30% year over year. We remain focused on advancing our Phase 1b study of R289 for the treatment of lower-risk MDS and completing the dose escalation portion of the study. We plan to initiate the dose expansion phase of the study and provide the updated data at a medical meeting later this year. For olutasidenib, we plan to initiate a new Rigel-sponsored Phase 2 study in recurrent glioma and continue to support our strategic collaborations with both MD Anderson and the Connect organization. Even with all these investments to advance our current and new pipeline programs, we expect to report positive net income for the full year of 2025. Moving on to slide thirty-four, I'm thrilled that Rigel Pharmaceuticals has reached this pivotal point in the company's history. Our implementation of our corporate strategy has brought us to a place where our commercial sales levels now allow us to grow the business in a profitable and sustainable manner. It's a really exciting time for the company. And with that, I would like to turn the call over to your questions.

Thank you. At this time, we'll begin our question and answer session. If you would like to ask a question, please press *1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press *2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from Yigal Nochomovitz with Citi. Please state your question.

Hi, guys. Thanks so much for taking the question. I have a few. The first one on the product guidance, I think you said $192 to $195 million. So using the fourth quarter as a base, could you just give a little more color as far as the comments there in terms of the range? It seems a little conservative. It looks like it's about a one to two percent quarter-on-quarter CAGR. Going off the Q4 base. That was my first question. Thank you.

Yeah. So the net revenue guidance is for $185 to $192 million. And the Q4 was $46.5 million of net product sales. That was aided by, as we said in our prepared comments, it was aided by inventory build in Q4, and we've seen this typically. That accounted for about $4.5 million of that $46.5 million of net revenues in Q4. So as you normalize that and you start to build Q1 through Q4, that creates the revenue guidance that we described. And that represents, at the midpoint, about a 30% year-over-year growth in net product sales.

Okay. Thanks, Dean. And then I'm curious on Rezlidia. Do you have any data from the field in terms of the duration of therapy there? I recall from a couple of years ago, there was some very, very good data you had showing the strength of that durability.

Hi, Yigal. Great question. This is Dave. We won't share any of that today, but what I can tell you is we have a lot of room to grow. At the end of the day, whenever you launch a product, and we're only two years into this, you're going to get a lot of later-line patients. And those patients are not going to have the duration of therapy that you would have seen in the clinical trial where they were probably in the second-line or third-line setting. And so, that's kind of where we are right now. So, obviously, we do believe our duration of therapy is a significant driver of adoption, but also a significant driver of carryover as we move forward. That's why I'm optimistic about our ability to grow as awareness grows, as we get more patients on therapy, and we get earlier patients on therapy, particularly those who've had first-line venetoclax. We think we can drive duration higher.

Thanks. And just one last one, if I might. Do you have any data as to the percent of patients that are on Gavreto by Rigel Pharmaceuticals versus Gavreto from the prior commercial sponsor?

I don't have specific data, but I can tell you, our goal was to transition every single patient that was on Gavreto over to Rigel Pharmaceuticals' product. I think the fact that we sold $8.1 million and that our demand grew from Q3 to Q4, and our run rate was higher than the previous run rate of $28 million last year, I think we achieved that. So I really don't think we lost any patients in the mix. And as a matter of fact, obviously, I think we're adding new patients. It's hard for us at this point in time to say new patients on brand versus new patients to Rigel Pharmaceuticals. We know they're all new patients to Rigel Pharmaceuticals. But we think we are getting new patients to brand because our demand continues to move up.

You know, Yigal, that was a pretty remarkable achievement, that transition, because you typically see a sale of a product from one company to another. And for probably six months, you see a lower sales base than originally before, and that wasn't the case here. So this is really pretty remarkable that we had achieved that, and we're really pleased with it. It also shows that we have the entirety of the team, medical affairs, market access, the sales organization really focused on the right things in getting those patients across. And so it really worked remarkably well. I'm actually incredibly impressed.

Got it. Thank you very much for taking the question.

Thank you. And our next question comes from Kalpit Patel with B. Riley Securities. Please state your question.

Hey, good afternoon and thanks for taking the questions. Maybe I want to start first with the TAVALISSE sales, the increase in the fourth quarter relative to the third quarter. Maybe comment on how much of that was an organic volume increase versus maybe any pricing increases that may have occurred?

I'm sorry. Can you repeat the last part of your question, Kalpit? You said volume versus price?

Yeah. Like the yeah. Exactly. This just you know, was this accounted for by any any price increases?

Yeah. We didn't have any price increase in Q4. So that was all volume. What I will say is we had you know, our highest quarterly demand ever that's been bottle shipped to patients and clinics. Matter of fact, it was the ninth consecutive quarterly high that we've hit. We also had a higher percentage of new patient starts or new patients versus existing patients kinda driving that volume in the fourth quarter. And so, again, as Dean said, we were also aided by some inventory build, which is typical in the last in the last quarter of the year. But demand definitely increased from Q3 to Q4 as the new patient starts.

And we did our press release highlight the unit volume, the demand volume, as Dave suggested, the demand or the bottles shipped to patients and clinics. That's really the key to the business. Those are the bottles that are going to patients. Incrementally, there's the bottles left in the distribution channels that we report. And those are inventory levels. For TAVALISSE, that inventory level benefit for Q4 was about $3 million. And that's in the $4.5 million I described. Again, TAVALISSE was benefited by about $3 million. That said, again, the demand is consistently growing, and that's the important measure of the business.

Okay. Okay. Great. And then maybe switching over to your glioma program, the plan Thirty I I know you're still working on the design there. But I'm curious on the strategy here. Are you are you gonna do a head to head study against vorasidenib or are you trying to maybe position your drug for a different grade glioma, maybe maybe a higher grade, a grade three or four? You said

Yeah. Thanks for the question. I I think at this point, it's still too early to comment on the design of the study. We've just kind of started our KOL discussions and ad boards and are working on that plan, but we'd certainly be happy to give you more information on this later in the year.

So for both R289 and olutasidenib in glioma, our plan is to later this year as we have some discussions with regulatory agencies and settle on what the plan is exactly. We'll come back to you and share that with you. It probably will be in the second half of the year.

Okay. Great. Thank you very much.

Thank you. And our next question comes from Joe Pantginis with H. C. Wainwright. Please state your question.

Everybody. Good afternoon. Thanks for taking the questions. So my first question is a two-parter for TAVALISSE, if you don't mind. So in the U. S, I guess, how would you describe well, first, can you describe the difference or the percentages of refills and the growing aspect of new prescriptions and what are you doing to help grow new prescriptions, say, today versus where you were, you know, one to two years ago. That's part one.

Yes. So I think great question, Joe. I I think as I said before, what we noticed in Q4, which was really nice, is that a larger percent of our patients and that's total patients on therapy, those who are carrying over from previous quarters, as well as new patients, a higher percentage was driven by new patients. As a matter of fact, the highest percentage we've ever seen. And so clearly, I think, you know, adoption's growing. I think some of the things that we're doing now that we've learned over the past is certainly, you know, targeting of clinicians is something we've spent a lot of time and effort to make sure that we're doing. Expanding reach through different channels is another thing that we're doing. And then, I think, the last part is you know, community practices play a lot a big role in the management of ITP. And I think, you know, we we we target the specific TPOs out there among the community practices to ensure that they're aware of our of ITP's unique value proposition. Or Will that help? Unique value proposition in ITP. Sorry. No. Of course. So and part two is

I guess, taking some of the components that you were just discussing. I want to discuss the ex U. S. Opportunities as you expand geographically. Are there any components that are unique to XUS Like you said, community centers, for example, how are they you know, how is the drug delivered there? Are are there differences in the initial lines of therapy? Any any particular components you can point to ex US that might differ from the US.

I think the best thing for me to do is kinda talk about how the US may be unique in that its use of TPOs and it particularly end plate is probably more driven by, you know, that community practice kind of buy and bill sort of mentality. And I think, you know, particularly in Japan, some of the differences there that they've seen is, you know, a a more a higher willingness to use combination therapy. And so I think there are some differences across the globe in how patients are treated and the way clinicians approach ITP management. But like I said, here in the US, it's a lot. It's treated You know, it it's not it's not a disease. It's a benign hematologic condition where if a hematologist oncologist sees this, you know, they're not gonna refer it. They're gonna treat it. So I think, you know, we have a very kind of diffuse model here in the US, which I think might be a little more concentrated in in other countries outside the US.

No. That's helpful. I appreciate that color. And then my last question, if you don't mind, is more of an infrastructure question. So as of right now, would you define your sales force as rightsized and as you look to add assets and are in early launch stages, you know, what would you envision as potential growth of the size of your sales force?

Thanks. Yeah. Great question, Joe. I I would say that, you know, what we've done with Rezlidia and Gavreto is ensure that we have synergies. And it's not just sales. Right? It's across the brand team. It's across market access, which is a a big component in in commercializing products these days, as well as our operational and analytical capabilities in business operations. So we have tremendous synergies there. But, you know, I'll just say that our our we're constantly looking at our impactable market and who how many customers we need to call on to ensure that we create impact positive impact on our brands in the market. And depending on the product we bring aboard, the subspecialists that might be involved, it could vary in terms of whether we would need to build sales support or not. And if it's something that is used primarily in the community or that I think we have the capacity to cover. But if it's something that's in a subspecialty that might that we're maybe not calling on today, then obviously, we need to address that.

But it's part of the assessment of the each of those individual opportunities as we decide to bring them in or not.

Sure. Sure. Thank you for all the comments.

Thank you, Joe.

Next question comes from Kristen Kluska with Cantor. Please state your question.

Hi. This is Diane on Kristen's line. Thank you for taking our questions. Could you talk a bit about your plan to initiate the expansion phase of the Phase 1 study of R289 this year? Any color you can provide here, particularly when you plan to start and how you go about choosing the doses?

Yeah. Thanks for the question. As you know, as I mentioned, we're currently enrolling in dose level six for dose escalation. So, first thing we're going to have to do is complete enrollment at that dose level and have a look at the safety and activity. Dose selection for expansion will be based on the typical things like safety, PKPD, and a little bit of activity. As you see on the you may have noticed on the slide, we plan to enroll up to twenty patients per arm because we really want to conduct a robust determination of a dose to carry forward and to for further clinical evaluation. So as we mentioned, we're looking forward to opening that later this year. And the exact timing of that, as I mentioned, will really depend on what's going on in dose escalation in this last cohort.

That's helpful. Thank you so much.

Thank you. And a reminder to the audience to ask a question now press *1. Our next question comes from Farzin Haque with Jefferies. Please state your question.

Hi. Thank you for taking my question. Also on R289, low-risk MDS program, so I wanted to ask on the Pfizer dose evaluations that are ongoing with split dosing, how are you setting ASH update in the second half? Then I have a follow-up.

Yeah. So as you noticed in our our and thanks for the question. Very interesting. As you noticed, during the course of the dose escalation phase, we changed tack from once daily to twice daily dosing. Because we think, biologically, it makes more sense to have more or less continuous suppression of inflammation as opposed to kind of an on-off on-off. So we're really looking forward to seeing the data from the BID dose levels. And related to the anticipated timing of the data presentation, well, I think our best opportunity is ASH. So we're anticipating having an opportunity there to present the updated study data.

Furthermore, keep in mind that we want to have four to six months of exposure in each of these patients in order to properly assess whether the product's working, its efficacy, importantly, its safety. So that does take some time to do that. So it, by necessity, has to be towards the end of this calendar year.

Got it. That makes sense. And then I will be waiting for the matured dose escalation data prior to meeting with the regulators for your registrational path?

I think we'll give some more information on that later as the data mature more.

But we won't wait till the end of the year to have that some interaction with them. The nice thing about fast track designation is that it allows them and us to work more closely together. That's really helpful.

Got it. Thank you so much.

Thank you. And there are no further questions at this time. I would like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Well, thank you. I'd like to thank you for joining this call today and your good questions and specifically for your continued interest in Rigel Pharmaceuticals. It's been a really monumental year for us. We're really proud of what we achieved in 2024 and incredibly excited about 2025. We have some significant things ahead of us, and I think we're really well positioned to execute successfully against them. Before we leave, I'd like to thank our employees for their continued interest in improving the lives of patients and for making 2024 such a successful year for us. So with that, look forward to updating you on future calls, and have a great day.