RIGL - NASDAQ

Greetings, and welcome to the Rigel Pharmaceuticals Financial Conference Call for the Third Quarter 2025. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce our first speaker, Ray Furey, Rigel's Executive Vice President, General Counsel and Corporate Secretary. Thank you, Mr. Furey, you may begin.

Welcome to our third quarter 2025 financial results and business update conference call. The financial press release for the third quarter of 2025 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, and subsequent filings with the SEC, including our Q3 quarterly report on Form 10-Q on file with the SEC. Any forward-looking statements are made only as of today's date, 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 CEO, Raul Rodriguez. Raul?

Thank you, Ray, and thank you all for joining us 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. On today's call, I will provide an overview of Rigel's business, along with our accomplishments and financial results for the third quarter of 2025. Starting on Slide 4, you will see an outline of Rigel's corporate strategy. Our strategic objectives are to grow our hematology and oncology business through commercial performance, pipeline expansion, coupled with financial discipline. Our continued execution of this strategy has led to another outstanding quarter for Rigel. For the third quarter, we reported total revenue of $69.5 million, including record net product sales of $64.1 million, a 65% year-over-year increase. Later in the call, Dave will provide more detailed information on our commercial performance for this quarter. Moving to our development pipeline. We continue to fund and advance our programs during the quarter. This includes our ongoing Phase Ib study of R289, Rigel's potent and selective dual IRAK1 and IRAK4 inhibitor that is being studied in patients with relapsed or refractory lower-risk MDS. We have completed enrollment of the dose escalation phase of the study, and we will present data from this phase in an oral presentation at the ASH Annual Meeting in December. In addition, we recently announced the first patient was enrolled in the dose expansion phase of the study, where we will compare 2 doses of R289 to determine the recommended dose for future registrational and other clinical studies. Moving on to olutasidenib. We will have 4 posters with data in patients with mutant IDH1 AML at the ASH meeting, supporting the use of olutasidenib in a range of difficult-to-treat mutant IDH1 AML patient populations. We continue to evaluate olutasidenib in other areas where IDH1 plays a role through various strategic collaborations. A fifth study with MD Anderson opened for enrollment in September. And in October, the first patient enrolled in the CONNECT Phase II TarGeT-D study, evaluating olutasidenib in patients with high-grade glioma. In addition, we are planning a collaboration with MyeloMATCH to evaluate olutasidenib in first-line AML and MDS. Lisa will provide the latest updates on our development pipeline later in the call. In terms of Rigel's own study in glioma, we are continuing to evaluate our options. Along with our commercial and development execution, we continue to pursue additional in-licensing deals or asset acquisitions that are synergistic with our capabilities, strategy and focus, allowing us to add additional avenues to achieve significant growth. Underpinning all our efforts is a continued emphasis on financial discipline, which allowed us to generate $27.9 million of net income in the third quarter and to increase our cash balance to $137.1 million. Now on to Slide 5, which illustrates the growth of our net product sales year-over-year. We have consistently delivered strong top line growth. We are accelerating this trend in 2025, already having generated $166.6 million in net product sales year-to-date, already surpassing net product sales for all of 2024. As a result of our outstanding commercial performance year-to-date, we are raising our 2025 revenue guidance. We now expect total revenue of $285 million to $290 million, an increase from the prior range of $270 million to $280 million. Our new guidance includes net product sales of $225 million to $230 million. This new 2025 outlook reflects anticipated growth of 55% to 59% compared to 2024, exceeding the growth rate that we have delivered over the last 4 years. Rigel has made tremendous progress in our unique approach that combines strong commercial execution, adding additional products through in-license or acquisition and financial discipline, all resulting in our ability to fund a potentially transformative internal development pipeline. We continue to focus on executing on our strategy to achieve significant long-term growth. Now with that, I will turn the call to Dave to discuss our commercial business in more detail. Dave?

Thank you, Raul. On Slide 7, you'll see our 3 commercial products, TAVALISSE, GAVRETO and RE

Thanks, Dave. I will now provide an overview of our pipeline progress and plans for the remainder of the year. I'm on Slide 12. Our hematology and oncology pipeline strategy is focused on the clinical development of R289, our potent and selective dual IRAK1 and IRAK4 inhibitor in lower-risk myelodysplastic syndrome, or MDS, and the expansion of olutasidenib beyond relapsed or refractory IDH1 mutated AML. Beginning with R289, our Phase Ib study in patients with relapsed or refractory lower-risk MDS is progressing well. Yesterday, we announced that we'll be providing updated data from the dose escalation portion of the R289 study in an oral presentation at the upcoming ASH Annual Meeting. I'll provide an update on the study shortly. As Raul mentioned, we're proud of our strategic collaborations to advance olutasidenib into additional therapeutic areas. With MD Anderson, olutasidenib is now being evaluated in 5 clinical studies in IDH1 mutation-positive AML and MDS and this maintenance therapy in IDH1 mutation-positive glioma by the CONNECT Cancer Consortium. We're also partnering with MyeloMATCH for a planned study in first-line AML and MDS. We're also considering additional Rigel-led studies, and we'll provide further updates on that as we have them. Rigel also remains focused on evaluating potential acquisition and in-licensing opportunities that strategically fit our hematology and oncology portfolio and infrastructure. We're focused on evaluating differentiated late-stage assets in hematology, oncology or related areas that are synergistic with our existing commercial portfolio. Now, we will spend a few moments on R289, our novel dual IRAK1 and IRAK4 inhibitor. First, on Slide 14, I'd like to talk about 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 from transfusions and subsequent organ dysfunction all negatively impact the patient. Therapies used in the upfront setting include erythropoiesis-stimulating agents, or ESAs, if patients are eligible or luspatercept. Luspatercept and more recently, imetelstat are also approved for ESA failure transfusion-dependent lower-risk MDS patients. Finally, hypomethylating agents or HMAs are also approved. However, the percentage of patients achieving transfusion independence is low. With 8-week transfusion independence rates approaching 40% with luspatercept and imetelstat, there is still a need for safe, effective therapies for transfusion-dependent lower-risk MDS patients that are relapsed, refractory to or ineligible for ESAs. Now I'll shift focus to the R289 program. On Slide 15, you can see the value proposition of R289 in lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the U.S. As mentioned on the previous slide, there's a high unmet need for therapies in this disease area, particularly for 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 normal 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. From the FDA, R289 has Fast Track designation for the treatment of patients with previously treated transfusion-dependent lower-risk MDS and orphan drug designation for MDS, giving the molecule an expedited regulatory pathway, potential priority review and 7 years of market exclusivity upon approval. Both of these designations underscore the agency's interest in this rare disease, the unmet need of the patient population and the FDA's willingness to collaborate with Rigel in the development of R289. In addition, R289 has thus far demonstrated a promising clinical profile in our Phase Ib study. At ASH in 2024, we presented promising preliminary safety and efficacy data from the Phase Ib study in elderly heavily pretreated patients. And we look forward to sharing updated data from the dose escalation part of the study soon in an oral presentation at this year's ASH meeting. On Slide 16, you'll see the design of our multicenter open-label Phase Ib study in patients with relapsed/refractory lower-risk MDS that are either transfusion-dependent or have symptomatic anemia. The study aims to evaluate the safety, PK and preliminary activity of R289 in this patient population as well as select a dose for future studies. We completed enrollment in the dose escalation part of the study in July, and the first patient in the dose expansion phase was enrolled last month. In this part of the study, up to 40 transfusion-dependent relapsed/refractory lower-risk MDS patients will be randomized to receive R289 doses of either 500 milligrams once or twice daily in order to select the recommended Phase II dose for future clinical studies. Once this occurs, we will evaluate R289 in a cohort of less heavily pretreated patients who are relapsed/refractory to or ineligible for ESAs. We anticipate that we will have sufficient data to make a decision on the recommended Phase II dose in the second half of next year, after which we would plan to have a follow-up discussion with the FDA about a potential pivotal study design. For now, updated dose escalation data using an October 28 data cutoff date will be shared in an oral presentation at the ASH meeting on Sunday, December 7. We're very pleased with the progress we've made this year with our R289 clinical program. Now, I'll transition to our strategic collaborations to evaluate olutasidenib in other cancers harboring IDH1 mutations. On Slide 18, we summarize our strategic alliance with the MD Anderson Cancer Center to advance olutasidenib more broadly into AML, MDS and beyond. A fifth study under the strategic alliance opened for enrollment in September. This study will evaluate olutasidenib in combination with co-targeted therapies in patients with relapsed/refractory IDH1 mutated myeloid malignancies harboring activated signaling pathway mutations. Enrollment also continues in the other 4 studies. On Slide 19, we're also proud of our collaboration with CONNECT, a global pediatric Neuro-Oncology Consortium, which is evaluating olutasidenib in adolescents and young adults with high-grade glioma, an area of high unmet medical need. In CONNECT’s TarGeT trial, a molecularly guided Phase II umbrella clinical trial for high-grade glioma, the Rigel-sponsored arm of the study, TarGeT-D, will evaluate a post-radiotherapy maintenance regimen of olutasidenib in combination with temozolomide, followed by olutasidenib monotherapy in newly diagnosed patients between 12 and 39 years of age with IDH mutation positive high-grade glioma. I'm pleased to report that this study enrolled its first patient in October. We, along with CONNECT, are excited about olutasidenib's potential to provide a much needed new treatment option to this underserved patient population. On Slide 20, I want to share with you our new partnership with MyeloMATCH, which will also evaluate olutasidenib in IDH1 mutated AML and MDS. MyeloMATCH is a group of precision medicine clinical trials for patients with MDS or AML led by the NIH and National Cancer Institute. This initiative is very compelling. Patients with newly diagnosed MDS or AML will go through an initial screening process before being assigned to a clinical trial evaluating targeted therapy for their specific disease mutational profile. Based on the promising data for olutasidenib in relapsed/refractory IDH1 mutated AML, the NCI was interested in studying olutasidenib in combination with other agents in patients with newly diagnosed IDH1 mutated AML and MDS. We're pleased to be participating in this important program and look forward to providing you with updates as the trial advances. Before I wrap up my remarks, I'd like to highlight Rigel's presentations at the upcoming ASH Annual Meeting in December, which you can see on Slide 21. For R289, we're pleased to share updated data from the dose escalation part of our Phase Ib study in lower-risk MDS. In the abstract published yesterday with data as of July 15, you'll see R289 continues to be generally well tolerated in a heavily pretreated patient population, the majority of whom were high transfusion burden at baseline. Preliminary signs of efficacy were observed with R289 doses of at least 500 milligrams once daily and higher. At the meeting, there will be an oral presentation of updated data using an October 28 data cut on Sunday, December 7. Additionally, 4 poster presentations for olutasidenib in patients with IDH1 mutated AML are planned. These presentations contribute to the growing body of data supporting the use of olutasidenib in patients with relapsed or refractory IDH1 mutated AML, including those who have previously been treated with a venetoclax-based regimen. Now, I'll pass the call to Dean to discuss our partnered program with Eli Lilly and our financial results for the quarter. Dean?

Thank you, Lisa. I'm on Slide 23. I'd like to provide a brief update on our collaboration with Lilly. Ocadusertib, the non-CNS penetrant RIPK1 inhibitor, previously referred to as R552, is currently being studied in an adaptive Phase IIa/IIb clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis. Enrollment in the Phase IIa study is ongoing. As most of you know, we also have a CNS penetrant program with Lilly, whereby Lilly was considering for preclinical development, a variety of RIPK1 inhibitor candidates pass the blood-brain barrier. In October, Lilly notified us that it will terminate the CNS disease program, which will become effective after 60 days. We continue to be very excited about our collaboration with Lilly as they are an ideal partner to explore the key role the RIPK1 inhibitors play in TNF signaling and pro-inflammatory necroptosis, which could support broad potential in RA, psoriasis and IBD. We also note that we are entitled to receive milestones and tiered royalty payments on future net sales of ocadusertib. Moving on to Slide 25. We reported net product sales of $64.1 million for the third quarter, a growth of 65% year-over-year, including TAVALISSE net product sales of $44.7 million, a growth of 70% year-over-year. GAVRETO net product sales of $11.1 million, a growth of 56% year-over-year. Lastly, we reported RE

Thank you, Dean. Moving on to Slide 27. Our 2025 results year-to-date are a culmination of the successful execution of the corporate strategy that we put in place several years ago, one aspect of which is to grow our commercial business. As you can see, we've reported strong year-to-date sales and the results -- because of this strong performance, we have raised our net product sales expectation for 2025 and now expect to generate growth of 55% to 59% year-over-year as compared to the 32% average growth that we have seen over the last 4 years. Moving on to Slide 28. For the remainder of 2025, we will continue our focus on driving our corporate strategy. We aim to increase sales of our commercial products and deliver on our updated revenue and profit guidance and also allowing -- and so allowing us to fund key development programs in our internal pipeline, and we are advancing these development programs. Enrollment in our dose escalation phase of our Phase Ib study of R289 in patients with lower-risk MDS is complete, and we look forward to presenting updated data at the -- of that study at the ASH meeting in December. Enrollment in the dose expansion phase of the study is now ongoing. For olutasidenib, our strategic collaborations are advancing with enrollment of the 5 MD Anderson studies and the CONNECT studies all ongoing. We continue to support the advancement of these strategic collaborations while working on the initiation of a new study with MyeloMATCH. And we're evaluating our options for a Rigel-led study in glioma. As we've done in the past, we are also evaluating new in-licensing and product acquisition opportunities to expand our product portfolio with synergistic late-stage assets, which could be funded through a combination of internal and external funds. In closing, Rigel has continued to demonstrate the strength of our business in the third quarter of 2025, and we aim to finish the year with a strong fourth quarter, supported by sustained financial discipline. I also want to reiterate our proven strategy has built Rigel into a profitable, growing, sustainable business that is well positioned for growth as we head into 2026. So with that, I'd like to thank you for your interest, and we will now open the call to your questions. Operator?

[Operator Instructions] Our first question today is coming from Yigal Nochomovitz from Citigroup.

This is [ Caroline ] on for Yigal. We were wondering how you see the competitive positioning of R289 in lower-risk MDS versus RYTELO. And maybe it's too early to say, but for the potential registrational study, would you do something similar to RYTELO's placebo-controlled study? And would you exclude patients who received RYTELO from your study?

I'll let Lisa to comment. I also have a comment on that.

Yes. I think that it might be a little bit too early. Thanks for the question, Caroline. Really good question. I think it might be a little early to speculate on that one. I mean we're -- first of all, now we're in a different patient population than imetelstat was. We're in patients that are much more heavily pretreated and have received HMAs. You'll recall that the patients in the Phase III randomized study for RYTELO had not received prior HMAs. So I would say that we're very pleased with the preliminary activity and safety profile that we're seeing thus far. It's definitely a bit too early to talk about our plans for a registration study, but we will -- I think our plan will be to get through dose expansion, fix the dose. As I mentioned, we will also then be opening a cohort of less heavily pretreated patients that are more akin to the recent luspatercept and imetelstat studies. So we'll have a look at the activity there, and then we'll decide on what our next plans will be.

Suffice it to say, we think that there's a broad range of opportunities for this product in lower-risk MDS after ESAs. And even after ESAs is an area where, as you may have seen in the slide, we tend to explore a bit more once we know the dose because that opens up an even larger opportunity set. So it's exciting to have that range of opportunity with this product, including before and after luspatercept potentially.

Next question today is coming from Joe Pantginis from H.C. Wainwright.

Great to see the launches continuing to be strong. So 2 questions first. So for 289, you mentioned the potential for looking at priority review. So I want to get maybe some profile views out of you guys with regard to maybe the level of data that you feel might be needed, the parameters for the profile of the drug, say, the importance for reducing transfusions. So I wanted to get your views there.

Yes. I think I'll take that. Thanks for the question, Joe. I think that given that we have the Fast Track designation, that really opens up potential for priority review, and that kind of underpins the comment there. So again, I think that we're going to have to see how the data continues to evolve in the dose expansion part of the study.

Got it. And then just quickly, this is a very important unmet medical need with oluta for the CONNECT study in glioma. Would you be able to provide some of the benchmarks we'd be looking to be with IDH1 mutations in this patient population?

Well, I think that's an interesting question as well. As far as I'm aware, this is a novel approach to taking patients that are post-chemo radiation, and this is more of a maintenance approach. So combined with temozolomide for 12 months initially followed by maintenance therapy. And there will be -- the comparison is versus a historical control. So I don't think there's specific data for -- in this maintenance setting.

So that's helpful in the sense that there might be a -- or considering a low bar of success there. So I appreciate the comments.

[Operator Instructions] Our next question is coming from Farzin Haque from Jefferies.

This is Amin on for Farzin. A couple of questions from us. First, you mentioned improvements in Q3 gross to net. What was the rate by brand and the expected Q1 and Q4 rates, especially for oral products under the Medicaid Part D redesign that has been improving access and affordability. And I have a follow-up.

Yes. I can start and then Dave can layer on top of this. We haven't provided specific guidance with respect to product by product or gross to net. We have said that we've had favorable gross to net dynamics with the patient, patient affordability. And therefore, as we think about our gross to net, there's a variety of factors that factor into it. We've got the mix, the type of patient and payer. We've got the different legislation like the IRA. And so all of those factor into the overall gross to net. It's been favorable the last several quarters now, and that's the level of detail we've given and again, not product by product. I don't know, Dave, do you have anything?

Yes. The only thing I would add is that our gross to net has a number of different factors like Dean said. But one of the things that we try to do is provide access to patients through patient services. And of course, we want to distribute our products to patients. And we have made significant strides in improving the efficiency of our -- both our patient services and distribution network, and that has also helped to improve our gross to net, which I think goes to what Raul is saying is our strategy is grow our sales and improve our efficiency, and that's exactly what we're doing. So I think all of these things are adding up to just a marvelous year for us.

Okay. Great. Helpful. And how are you setting expectations for the updated data at ASH for R289 in lower-risk MDS patients? How much data beyond the abstract do you plan to present?

Yes, I can take that one. Thanks for the question. So we're going to be -- with the October 28 data cutoff date that I mentioned, we will have 16 weeks of follow-up on all of the patients. So all of the patients -- that includes all the patients in the 500-milligram BID dose level. So that's all I'm going to say on that one. Yes.

So really, it's a good data set with that final dose group, having data from that final dose group, which we're eager to share.

We reached the end of our question-and-answer session. I'd like to turn the call back over to Mr. Raul Rodriguez for any further closing comments.

Well, thank you. I appreciate your questions. And thank you, everyone, for joining us on the call today and your continued interest in Rigel. So far, 2025 has been a tremendous year for both our commercial portfolio and advancing our development pipeline. And we look forward to sharing that data at the ASH meeting that we mentioned on R289 in December. To our employees, I'd like to thank you for your continued dedication to the company. It is through your innovation, integrity and your commitment to patients that we've reached this successful place. So I look forward to updating you on our future progress and all have a good afternoon, evening.