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…

Thank you, Raul. On Slide 7, you'll see our 3 commercial products, TAVALISSE, GAVRETO and REZLIDHIA. Moving to Slide 8. We are thrilled to report another excellent quarter from our commercial portfolio, marked by strong year-over-year growth and an all-time high in revenues in the third quarter of 2025. The slide shows how our quarterly and annual net product sales have increased since 2021. We've grown each quarter's sales over the previous year, and that growth continues. In the third quarter of 2024, we reported $38.9 million. And now for the third quarter of 2025, we generated a record $64.1 million, an increase of 65%. Our third quarter commercial portfolio net sales reflect increased demand through carryover from both improved patient affordability that we started to experience earlier in the year and new patients, which was also augmented by favorable gross to net dynamics. As Raul mentioned, our year-to-date 2025 revenue has surpassed our 2024 full year revenue. And on a trailing 12-month basis, we've exceeded $200 million in net product sales, illustrating that our focus on growing our commercial portfolio is being executed in line with our strategy, a remarkable achievement by the team. Our commercial team has been dedicated to execution and driving momentum for our commercial portfolio, and I thank them for their continued efforts. Slide 9 shows a summary of our commercial performance by product. First on TAVALISSE, the cornerstone of our business, I'm pleased to report a record quarter in which we generated $44.7 million in net product sales, an increase of 70% compared to the third quarter of 2024. This growth was driven by increased demand and favorable gross to net dynamics. For GAVRETO, we delivered $11.1 million in net product sales in Q3, an increase of 56% compared to the third quarter of…

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…

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 REZLIDHIA net product sales of $8.3 million, a growth of 50% year-over-year. Our net product sales were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance and other allowances of $21.6 million. We also reported $5.4 million in contract revenues from our collaborations for the third quarter. primarily consisting of $3.1 million of revenue from Grifols, $1.8 million of revenue from Kissei and $200,000 of revenue from Medison related to delivery of drug supplies and…

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.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.