Greetings, and welcome to the Rigel Pharmaceuticals Financial Conference Call for the Fourth Quarter and Full Year 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 fourth quarter and full year 2025 financial results and business update conference call. The financial press release for the fourth quarter and the full year 2025 for the -- and full year 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, 2025, 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 Chief Executive Officer, Raul Rodriguez. Raul?

Thank you, Ray, and thank you all for joining us today. Also with me 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, our accomplishments for the fourth quarter and full year 2025 as well as our strategic initiatives to drive growth. Beginning on Slide 4. I will outline Rigel's transformational growth strategy in hematology and oncology. For those of you less familiar with Rigel, our strategy is built around 4 core strategic objectives: grow our commercial business, expanding our portfolio through in-licensing or acquisition, advancing our clinical development pipeline and maintaining financial discipline. These 4 pillars are interlocking and collectively drive Rigel's long-term growth. Today, I will highlight how we've executed on this strategy since 2020, building Rigel into the profitable company we are today and how this framework positions us for continued growth in the years ahead. Moving on to Slide 5. Let me begin by outlining the transformation at Rigel over the last 5 years. In 2020, Rigel was a single product company. TAVALISSE was our only approved product indicated for the treatment of adult chronic ITP. Our development pipeline was limited, and the company was operating with negative cash flows. Now at the end of 2025 and now entering into 2026, we are fundamentally a different company. We now have 3 commercial products, TAVALISSE, REZLIDHIA and GAVRETO, approved for 4 different indications. Our development pipeline is led by R289, a dual IRAK1/4 inhibitor discovered at Rigel. R289 is currently being evaluated in patients with lower-risk MDS, a potentially large commercial opportunity with significant unmet need. R289 offers a novel mechanism, attenuating the hyperinflammatory signal present in lower-risk MDS and so may offer a new…

Thank you, Raul. On Slide 10, you'll see our 3 commercial products, TAVALISSE, GAVRETO and REZLIDHIA. Moving to Slide 11. We are thrilled to report full year results for 2025 and how our net sales have consistently grown over the last 5 years. In 2021, TAVALISSE was the only product in our portfolio, and we generated $63 million in net sales. In 2022, we continued to grow TAVALISSE and brought REZLIDHIA into our portfolio, launching the product in December. In 2023, the addition of REZLIDHIA and continued growth of TAVALISSE propelled us over the $100 million annual sales threshold. Then in 2024, we continue to grow those sales and added our third brand, GAVRETO, to our portfolio. And in 2025, we exceeded our expectations, delivering $232 million in net product sales, an increase of $87 million or 60% compared to 2024. This outstanding year-over-year growth was primarily driven by increased demand across our portfolio, which included the onetime favorable effect from increased patient affordability during the year and favorable gross-to-net dynamics, partially offset by lower inventory levels. To summarize, our strategy of focusing on both product and portfolio growth over the last 4 years has nearly quadrupled our net sales. And over just the last 2 years, that growth has accelerated as we've more than doubled sales. Our strategy to grow our commercial business is working, and I want to thank the entire organization for collaborating as one Rigel team to create such outstanding results. Slide 12 shows a summary of our fourth quarter commercial performance by product. For the fourth quarter, we generated a record $65.4 million, an increase of $18.9 million or 41% compared to the fourth quarter of 2024. First on TAVALISSE, I'm pleased to report another record quarter in which we generated $45.6 million in net…

Thanks, Dave. I will now provide an update on our progress over the last quarter and plans for the year ahead. I'm on Slide 15. Our current hematology and oncology focus areas are the clinical development of R289, our potent and selective dual IRAK1 and IRAK4 inhibitor and our strategic collaborations with academic partners to evaluate olutasidenib in clinical settings beyond relapsed/refractory IDH1 mutated AML. Our Phase Ib study of R289 in patients with relapsed or refractory lower-risk myelodysplastic syndrome, or MDS, is progressing well and updated data from the dose escalation part of the study was recently presented in an oral session at ASH. I'll provide an update on that study as well as our planned next steps for R289 shortly. For olutasidenib, we have a number of strategic collaborations to study olutasidenib in additional therapeutic areas. Through our collaboration with MD Anderson, olutasidenib is being evaluated in 5 clinical studies as monotherapy or combination therapy in patients with a variety of IDH1 mutation-positive hematologic malignancies, including AML, higher and lower-risk MDS, chronic myelomonocytic leukemia, or CMML, and its post-transplant maintenance therapy. In addition, a study of olutasidenib in combination with co-targeted therapy in patients with relapsed or refractory AML with additional signaling pathway mutations is underway. Our second collaboration with the CONNECT Cancer Consortium and the Phase II TarGeT-D study is evaluating olutasidenib in combination with temozolomide followed by olutasidenib monotherapy as maintenance treatment in newly diagnosed pediatric and young adult patients with IDH1 mutation-positive high-grade glioma. First patient was enrolled in the study in October. Lastly, we're also partnering with the National Institutes of Health and National Cancer Institute's MyeloMATCH Precision Medicine Trial Initiative. The planned study will evaluate olutasidenib in first-line IDH1 mutated AML and MDS. We're excited about olutasidenib's potential to provide a new treatment…

Thank you, Lisa. I'm on Slide #29. We reported net product sales of $65.4 million for the fourth quarter, a growth of 41% year-over-year, including TAVALISSE net product sales of $45.6 million, a growth of 47% year-over-year, GAVRETO net product sales of $10.2 million a growth of 27% year-over-year. Lastly, we reported REZLIDHIA net product sales of $9.6 million, a growth of 29% year-over-year. Our net product sales were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance and other allowances of $19 million. We also reported $4.4 million in contract revenues for the fourth quarter, primarily consisting of $3.4 million of revenue from Grifols related to the delivery of drug supplies and earned royalties, $300,000 of revenue from Kissei related to the delivery of drug supplies, $300,000 in government contract revenues and $200,000 of revenue from Medison related to earned royalties. This brings our total revenue for the fourth quarter to $69.8 million. Moving to Slide 30. For the fourth quarter of 2025, our cost of product sales was approximately $6 million. Total costs and expenses were $46.6 million compared to $40.9 million for the same period in 2024. The increase in costs and expenses was mainly due to increased research and development costs, driven by the timing of clinical activities related to R289 and olutasidenib and higher personnel-related costs. Fourth quarter results include a nonrecurring income tax benefit driven by the release of the valuation allowance on our deferred tax asset. For reference, the valuation allowance is recorded against deferred tax assets when it's more likely than not that those assets will not be realized. Given our track record of profitability, projected operating income and positive outlook, we concluded that a release of the valuation allowance was appropriate as of December 31, 2025. While this release impacts…

Thank you, Dean. Moving on to Slide 31 as we wrap up. Our key strategic objectives for 2026 are clear: grow our commercial business, pursue in-license opportunities to further expand our portfolio and thus enhance cash generation, advance our development pipeline, particularly R289 and maintain financial discipline as we deliver another year of top line growth and positive net income. We are especially excited about our opportunity for R289. This year includes several anticipated milestones in lower-risk MDS, including dose expansion phase data expected at the end of the year. In addition, we are evaluating additional opportunities for R289, and we look forward to sharing further updates later in the year. In closing, the focused execution against our 4 strategic objectives has driven transformational growth since 2020 and culminated in a record performance in 2025. We believe this momentum positions us well for a strong 2026 as reflected in our financial guidance and for the continued value creation the rest of this decade. With that, I will turn the call over to the operator for questions. Operator, we're now ready for questions.

[Operator Instructions] Our first question comes from the line of Joe Pantginis with H.C. Wainwright.

So first on the approved product growth. So when you're looking at TAVALISSE, what do you feel the incremental growth drivers can be here right now since this is a relatively mature product? And then for GAVRETO, the way you described it, obviously, was a stable contributing product. I guess, I would ask my question this way, how are the reintroduction efforts going to be able to look towards potential growth for GAVRETO?

Thank you, Joe. I'll ask Dave to comment on those 2 questions.

Yes. Thanks for the question, Joe. Obviously, last year was an incredible year of growth with TAVALISSE. It was our single largest year of growth ever. And as I said, it was in my prepared remarks, demand was a driver of our growth for all of our products last year. But I will say that, that was helped by a onetime favorable effect from increased affordability, which means that the elimination of the coverage gap happened last year. And with that came an ability for patients with Medicare Part D to have improved affordability to move on to TAVALISSE. So that helped certainly last year, but that was a onetime effect. And then obviously, we won't see that kind of effect happening in future years. But we're going to do what we've always done with TAVALISSE, which is continue to grow new patient starts. Look, Joe, it's a market of more than 14,000 patients in the second line and later setting. There's a number of treatment options out there, but a lot of doctors treat ITP. And so our goal is to make sure we get to them with the message that TAVALISSE is an outstanding alternative for patients. They can take this drug and it can keep their platelet levels where a clinician and the patient wants to have them and they can go on living their life. And so what we try to do is to spread that message as farm wide as possible. We've done some things last year that were very good to spread that message like even we piloted a virtual sales team because that's both efficient and it's effective in kind of generating messages further than your -- your field team, and we saw some really good results with that. So those are the kinds of things we're going to focus on in 2026 and beyond to continue to grow new patients starts with TAVALISSE. We think that's really important. And then with GAVRETO, I think, as I said, in the prior company's hands, this was about a $28 million to $30 million product, and we generated over $40 million last year. And we think that's just great. It shows -- and a big part of our growth, right, was having GAVRETO for a full year versus just a half a year in 2024. Obviously, we're not going to have that advantage in 2026, but it shows how our strategy of in-licensing and acquisition is working. And so we'll continue some very targeted efforts there. We think there's some great opportunities with GAVRETO that we're going to continue to do. And as we've always done, try as hard as we can to continue growing our portfolio sales year-over-year.

Our next question comes from Yigal Nochomovitz with Citi.

I just had a few. I'm curious on your decision with regard to the dosing, the 500 QD versus 500 BID, pros and cons as far as which you would be more comfortable taking forward? What's your -- do you have a sense as to which would be more likely based on everything you know today? And then anything you can say with respect to BD in terms of getting closer to another asset? I know you obviously are looking at things all the time, and there's a lot to digest in terms of what the right fit is for your -- for the business. So if you could just comment as far as how that's going, please?

Thank you, Yigal. I'll ask Lisa to comment on the dose, and I'll take the BD question.

Thanks, Raul. Thanks for the question, Yigal. So at the time we selected the doses for comparison in dose expansion, and we wanted to be compliant with the FDA's Project Optimus. So we do the most robust dose selection possible. We compared the lowest effective dose, which was 500 milligrams daily with the highest safe dose at that time was 500 milligrams BID. So I think that we don't really have a preference where we'll see what unfolds with the data. One could think that with BID dosing, you may have more tonic suppression of inflammation instead of kind of peaks and troughs. So that's one factor in favor of the BID potentially. But since both doses were active, as you saw with the ASH data, we're going to wait this one out.

Yigal, on your second question, we are looking at a great number of opportunities out there in hematology/oncology. And we're in a fortunate place that many opportunities that are out there are in the order of magnitude in terms of the size that would be appropriate for us. And we're evaluating a multitude of opportunities on a constant basis. The difficulty is projecting exactly when one will fall into place and we get to a yes and we sign the deal. But when you have enough balls in the air, one eventually does fall into place. We succeeded in acquiring GAVRETO a couple of years ago in '24, and we succeeded acquiring REZLIDHIA couple of years before that in '22. So '26 is a year that we hope to accomplish this. If not, we certainly would make a big effort to try to get it done. Like I said, we're looking for late-stage opportunities that are about ready to launch that is NDA ready or NDA filed or already approved, where a company of our size and our scale of business could add value to the launch of the product. And there's a number of things out there that look attractive for us. And so we're continuously work towards that, and we'll tell you exactly when it is when we have a press release related to this.

Our next question comes from the line of Ashleigh Acker with Piper Sandler.

This is Ashleigh. I'm on for Ally Bratzel at Piper Sandler. So I just had one on R289. So we know you're launching the exploratory study in post ESA or treatment-naive MDS. We know that this represents a really significant earlier line population. So can you just remind me what the strategic rationale is for exploring this population now rather than waiting for a registrational trial? And also, what kind of benefit are you aiming to show in this population? Anything that you're able to frame in terms of response rates or durability? Just to have us thinking about this would be really helpful.

Thanks for the question, Ashleigh. This is Lisa. So -- the reason that we're going to do that is because we -- if you think about that treatment landscape slide that I talked through, we are now in patients that are more heavily pretreated, high transfusion burden. So this is a really unique population where we started compared to the other agents on the market that, for example, luspatercept and imetelstat. So they generated their data in a patient population that were more or less post ESA or ineligible for ESA transfusion-dependent patients. So we started here. We're very encouraged by the data that we're seeing thus far, given the refractory nature of the patients. And we have -- we're optimistic that as we move the drug into an earlier line of therapy, that activity may be even better. So this is in the plans. Once we get the recommended Phase II dose, that's why we want to open that cohort of the less heavily pretreated patients to evaluate 289 in that patient population and get some preliminary data.

On your second question, as you -- as Lisa said, the currently approved products have real limitations, luspatercept and imetelstat 38%, 40% response rates in fairly early patients, HMA is 18% to 20%. That leaves a lot to be desired in terms of products that provide a benefit. And having an agent like 289 that has a very different mechanism than all of those, we think will be a real benefit to patients with low-risk MDS already in very refractory patients, as you heard Lisa, we work in about 33% of the patients tested that are above 500 milligrams transfusion-dependent and evaluable. Now small numbers still, but that's a pretty nice early result in very refractory patients. So we're optimistic that we could have a benefit that's broader than that, especially if we move earlier and especially given that there's not that attractive a metric out there that we can't improve on.

Our next question comes from the line of Farzin Haque with Jefferies.

I have a couple. Like for 289, where are you at with enrollment in the dose expansion phase? And have there been any challenges in finding patients? And then can you clarify how much follow-up would you need before you meet with the regulators for the path forward?

Okay. Thanks for the question, Farzin. I'll take that. So the enrollment is progressing. As I mentioned, we are aiming to select the recommended Phase II dose in the second half of the year, and we're on track to do that. In terms of the follow-up that we would need as before to be eligible for evaluation of red cell transfusion independence, the patients should have been treated for at least 16 weeks before we can make that determination. So it's going to be a combined look at PK safety and efficacy data in terms of recommended Phase II dose selection.

Got it. And then quickly on the net product sales guidance, it seems a bit conservative given the growth we saw in 2025. Are there any specific inventory shifts or competitive headwinds or conservative market access assumptions that are factored into this outlook?

Yes, that's a good question, Farzin, and I'll be happy to take that. Listen, as I said, we're just absolutely thrilled that we just grew $87 million, generating $232 million last year. And as I said in my prepared remarks, that was driven by demand growth across all the brands, and it was helped by a onetime favorable effect from improved patient affordability during the year and favorable gross to net dynamics. And as I just said, you should recall that we had GAVRETO for the full year versus half a year in 2024. And so we had just a phenomenal year, and you put everything together, and that's what generated $87 million or 60% growth. So moving to 2026. I'm telling you, we're really quite pleased to announce that on top of that really strong and very remarkable growth last year, we're still expecting double-digit growth. So we wouldn't call that a low expectation, but rather a challenging one, given that we're working off a much higher base now with all 3 brands and we don't have that onetime favorable effect of improved affordability. And we won't know -- we improved gross to net so much last year that it's really going to be difficult to have that kind of impact again in 2026. We still work on it, but there are things that are out of your control as well. So look, here's what we have to do. We've got to continue to drive new patient starts with TAVALISSE after it just generated its single largest year of growth ever in its history. And we have to realize this outstanding opportunity we still believe we have with REZLIDHIA. And those are big challenges for us as an organization, but we think we have the ability to do that. So again, I would say we're actually setting high expectations after a very remarkable year, and we'll work every single day to try to achieve those expectations. But I certainly wouldn't call them muted by any stretch of the imagination.

I would have to agree with you, Dave. The onetime effects of last year got us to a very different level than we had ever been historically. And this level, we're maintaining and building on into this year. It's not going to be the outstanding growth over last year. It's going to be incremental growth in the double digits, but it's not going to be like 60%. That's not the case. The patient affordability helped a lot last year, though it's still affordable this year. That is beneficial to us. So we're going to maintain those level of sales and plan to growing those. One thing I should note is because we got to this level of sales last year and again, this year, it means we're profitable. That's a fantastic place to be, generating cash as a business, and we have a great place to invest that cash in terms of opportunities like 289 that I think are truly transformational.

Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald.

Most of them have been asked but maybe I could just ask one on the sales force, given the big jump that you've seen in revenue in the last year or so, curious if you have any plans to put the gas on the sales force and expand that even more? Or do you feel by now, most of the physicians out there have a pretty good sense of what you're doing and enough touch points?

Yes. So great question, Kristen. Listen, we look at the impactability of all of our brands consistently. We look at where we have the most opportunity to grow. And certainly, our sales force has been pivotal to spreading the word about TAVALISSE, REZLIDHIA and making sure people understood that it's now available -- that GAVRETO is now available for Rigel. And so we focus them on where the opportunity is. And certainly, we're constantly looking at whether we're having the right promotional effectiveness out there in the field. But we think we're rightsized. We're calling on the right clinicians. We've got a lot of data. That's one of the areas that we've really improved on over the last several years, but particularly last year, we've really had a strong emphasis on really looking at our data sources and really understanding where the best opportunities are to generate business. And we've even incorporated some very innovative tools to target where that business is. So I think we're well positioned on our sales team to realize the opportunities that are out there. But it is challenging to access clinicians. I'll say that. Over and over again, I mean, our team is superb at it, but it is not easy, and it just gets harder to access clinicians. So that's why we really focus on kind of where the business opportunity is. If there's an IDH1 patient there, that's where we're going with the REZLIDHIA message. And we're really trying to be very, very thoughtful about where we can provide impact with a message like that. So to answer your question, we're not looking at expanding the sales organization at this point in time. As a matter of fact, we're looking at ways to make sure we're even more impactful with the resources we have.

There are no further questions at this time. I'd like to pass the call back over to Mr. Raul Rodriguez.

Thank you very much, operator. Everyone, thank you for joining us on the call today and for your continued interest in Rigel. I'd also like to take the opportunity to thank our employees for their ongoing dedication. Their innovation, integrity and steadfast commitment to patients has driven our evolution as a company and has expanded access to important therapies for those living with hematology and oncology conditions. 2025 was a tremendous year for Rigel, marked by strong growth in our commercial portfolio, advancement of our development pipeline and a solid financial position. These traits put us in a favorable and very select position within the biotech industry, and we look forward to updating you on our continued progress. Thank you, and have a good evening.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.