Rigel Pharmaceuticals Inc

NASDAQ:RIGL

Q4-2025 Earnings Call

[Operator]

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.

[Raymond Furey, executive]

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?

[Raul Rodriguez, executive]

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 approach to lower-risk MDS and potentially other diseases. Later in this presentation, Lisa will speak to the encouraging results from our Phase Ib study that were presented at the ASH meeting in December.

And our financial position is fundamentally different today. Rigel is profitable and has been since the third quarter of 2024. Since then, we have increased our cash position by more than $100 billion. This progress reflects disciplined capital allocation, thoughtful portfolio expansion and consistent execution across operations.

Now looking ahead to 2030, we plan again to be a fundamentally different company. We are building on the commercial momentum of our 3 commercial products while selectively pursuing late-stage in-licensing and acquisition opportunities to further expand our commercial portfolio. At the same time, we will continue to advance R289 in lower-risk MDS and potentially additional indications. These indications will be areas of significant unmet need, and so our large commercial opportunities that again would be transformational for Rigel.

As illustrated on Slide 6, Rigel has delivered strong net product sales growth since emerging from the COVID pandemic. Based on the midpoint of our 2026 net product sales guidance of $260 million, we are achieving a compound annual growth rate of approximately 35% since 2022. This performance reflects strong commercial execution and successful portfolio expansion.

What is even more compelling is the opportunity ahead, driven by the growth of our current products, additional in-licensed or acquired products and particularly R289 in lower-risk MDS and other indications. These programs represent potentially billion-dollar opportunities that will expand our commercial portfolio in the 2030s and beyond. This strategy creates a clear road map for sustained growth and long-term shareholder value creation.

Before I turn the call over to the rest of the team to discuss our other strategic objectives, I want to briefly highlight our approach to in-licensing and business development. Moving to Slide 8. We have a proven track record in business development, demonstrated by our acquisitions of REZLIDHIA and GAVRETO. Leveraging our existing commercial infrastructure, we efficiently incorporated both products into our portfolio with limited integration costs and operating expenses. As a result, a significant portion of those products revenue have contributed to our profitability and cash generation.

As we evaluate future opportunities, we are focused on differentiated assets in hematology, oncology or closely related areas. We are seeking late-stage assets that have completed registrational trial, are NDA ready or under review or are already commercially available. These late-stage assets are targeted opportunities that would be launched within the next 3 years, ideally no later than 2028, after which we will begin to shift our focus to the potential launch of R289 in lower-risk MDS and other potential indications.

Consistent with our prior transactions, we are prioritizing assets that leverage our existing commercial infrastructure, which will enable operational efficiency and thus be rapidly accretive and drive sustained cash generation for the company.

And with that, I will turn the call over to Dave to discuss our strategic priority of growing our commercial business. Dave?

[David Santos, executive]

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 product sales, an increase of 47% compared to the fourth quarter of 2024. TAVALISSE was approved in 2018 and is our cornerstone product, now reaching $45 million in quarterly sales, a true achievement for the team.

For GAVRETO, we delivered $10.2 million in net product sales, an increase of 27% compared to the fourth quarter of 2024. GAVRETO became commercially available from Rigel in mid-2024. And following the successful integration of this product, we were able to maintain the sales level that was generated in the prior company's hands, and we have now grown it to be a stable contributing product in our portfolio.

And for REZLIDHIA, we reported $9.6 million in net product sales, an increase of 29% compared to the prior year period. Since in-licensing this product in 2022, it's grown to nearly $10 million a quarter, substantial growth from a year ago, and we believe there is more growth coming. We have confidence that there is significant opportunity for REZLIDHIA because we believe it has important differentiators in the IDH1 mutated relapsed or refractory AML patient population, namely our compelling data demonstrating durable responses and our consistent efficacy results in the challenging to treat post-venetoclax setting.

Finally, on Slide 13, we generated $4.4 million in revenues from collaborations in the fourth quarter, driven by the availability of TAVALISSE in global markets. TAVALISSE is commercially available in Europe under the brand name TAVLESSE, in Japan and South Korea and Asia and in Canada and Israel via our partners, Grifols, Kissei and Medison. Our partners continue to pursue regulatory approvals for TAVALISSE in new markets. And we continue to work on expanding access to our products in markets outside of the U.S.

For REZLIDHIA, in 2024, we expanded our relationship with Kissei to include several countries in Asia for all potential indications, and we entered into an exclusive license agreement with Dr. Reddy's for all potential indications throughout Dr. Reddy's territory. These partners are now in the process of advancing REZLIDHIA in preparation for future potential regulatory submissions. We are pleased that access to our products is expanding outside the U.S.

I'll now pass the call over to Lisa to provide an update on the advancement of our development pipeline. Lisa?

[Lisa Rojkjaer, executive]

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 option in these underserved patient populations and look forward to seeing the data that these studies generate in the future.

Now I'll discuss R289, our novel dual IRAK1 and IRAK4 inhibitor. Let's start with the treatment landscape for lower-risk MDS. I'm now on Slide 17. 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 patients. Finally, while hypomethylating agents or HMAs are also approved, 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.

On Slide 18, you'll 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. And 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 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.

R289 has Fast Track designation for the treatment of patients with previously treated transfusion-dependent lower-risk MDS and orphan drug designation for MDS from the FDA, 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. R289 has thus far demonstrated a promising clinical profile in our Phase Ib study with encouraging safety and preliminary efficacy data that were highlighted recently at ASH in December.

On Slide 19, I'd like to quickly review the design of our multicenter open-label Phase Ib study in patients with relapsed/refractory lower-risk MDS, which aims to evaluate the safety, tolerability, PK and preliminary efficacy of R289 in this patient population as well as select a dose for future studies. The dose escalation phase evaluated 6 different R289 dosing regimens administered once or twice daily using a modified 3+3 design.

In the dose expansion 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. The first dose expansion patient was dosed in October.

We anticipate that we will have sufficient data to make a decision on the recommended Phase II dose in the second half of this year. Once we've selected the dose, we will evaluate R289 in a cohort of less heavily pretreated patients who are relapsed/refractory to or ineligible for ESAs.

Now I'd like to walk you through updated safety and efficacy results from the Phase Ib study with the data cutoff date of October 28 that were presented at ASH. On Slide 21, you will see the characteristics of the 33 patients enrolled in the dose escalation part of the study. The median age was 75 and the patients were heavily pretreated with a median of 3 prior therapies with around 70% having received prior luspatercept and HMAs. In addition, the majority of the patients had a high baseline transfusion burden. These characteristics are really representative of the lower-risk MDS population with the highest unmet medical need.

Moving to Slide 22, we'll review the safety findings. Overall, R289 was generally well tolerated with a low incidence of Grade 3 or 4 cytopenias and infections. There was one dose-limiting toxicity reported, a Grade 3/4 AST/ALT increase at the 750-milligram daily dose level and no evidence of dose-dependent toxicity across the other dose groups.

On Slide 23, the swimmer plot shows an overview of transfusion events by dose group, starting with the lowest dose group, 250 milligrams daily at the top. Red cell transfusions occurring over at 16 weeks prior to start of R289 are shown to the left of the colored bars, establishing the baseline transfusion frequency for each patient. All patients were transfusion dependent, except for 2.

The median time on therapy was 5.5 months, ranging from 0.9 months to nearly 28 months of treatment. To be evaluable for hematologic response assessment, patients must have been treated for at least 16 weeks. No response has occurred at 250 milligrams once or twice daily. Of 18 evaluable patients receiving dose levels of 500 milligrams daily or higher, 6 patients or 33% achieved red cell transfusion independence or RBC-TI, lasting for 8 weeks or longer.

In 4 patients, RBC-TI lasted for more than 16 weeks and for 3 patients for more than 6 months. The median duration of RBC-TI was around 23 weeks, ranging from 9 weeks up to more than 24 months. Also, the median time to onset of RBC-TI was about 2 months, which is also encouraging. While this is a small data set, we're encouraged by these results given the highly refractory nature of these patients.

Slide 24 presents a summary of the patients achieving RBC-TI. All patients had received 2 or more prior therapies, some had received experimental therapies and 5 of the 6 had received prior HMAs. For these patients, peak hemoglobin increases ranging from 2.9 to 6.1 grams per deciliter were also observed, indicating the potential of R289 to improve anemia.

In summary, R289 was generally well tolerated with an encouraging safety profile and promising preliminary efficacy in an elderly, heavily pretreated lower-risk MDS patient population.

On Slide 25, I will review the next steps for R289. We aim to complete enrollment of the dose expansion phase of the study and selection of the recommended Phase II dose for future studies in the second half of this year. We anticipate sharing top line data from the dose expansion phase by the end of the year. Once the recommended Phase II dose has been selected, we will evaluate R289 in a cohort of less heavily pretreated patients who are relapsed/refractory to or ineligible for ESAs in the same study.

In addition, upon completion of the Phase Ib study, we plan to follow up with the FDA to discuss a potential registration study. With its mechanism of action, we believe that R289 has potential in other indications where the pro-inflammatory cascade plays a role, and we'll provide more details as our plans progress.

Now turning to our partnered program with Eli Lilly. On Slide 27, I'd like to provide a short update on ocadusertib, the non-CNS penetrant RIPK1 inhibitor previously referred to as R552 that is being evaluated in an adaptive Phase IIa/IIb clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis. During the fourth quarter, enrollment in the Phase IIa part of the study was completed, and the trial is ongoing.

Now I'll pass the call to Dean to discuss our financials. Dean?

[Dean Schorno, executive]

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 reported GAAP net income and earnings per share, it does not affect our cash position or our day-to-day operating performance. In this context, for the fourth quarter, income before income taxes was $22.7 million compared to $15.2 million for the same period of 2024. Benefit from income taxes was $245.4 million in the fourth quarter, which was primarily driven by $245.9 million of noncash deferred income tax benefit, partially offset by state tax expenses.

We reported net income of $268.1 million for the fourth quarter compared to $14.3 million for the same period in 2024. For the full year, cost of product sales was $19.6 million. Total costs and expenses were $168.8 million compared to $155.1 million for the full year of 2024. The increase in cost and expenses was primarily due to increased research and development costs, driven by the timing of clinical activities related to R289 and olutasidenib, higher personnel-related costs and higher cost of product sales.

Income before income taxes was $121.8 million for the year compared to $18.4 million for the full year of 2024. Benefit from income taxes was $245.2 million for the year, which was primarily driven by $245.9 million of noncash deferred income tax benefit, partially offset by state tax expenses. We reported net income of $367 million for the full year compared to $17.5 million for the full year of 2024. We ended the year with cash, cash equivalents and short-term investments of $155 million compared to $77.3 million as of the end of 2024.

Now for our financial outlook for 2026. We expect total revenue in the range of approximately $275 million to $290 million, comprised of approximately $255 million to $265 million in net product sales and $20 million to $25 million of contract revenues. We also anticipate reporting positive net income for the full year while funding existing and new clinical development programs.

In closing, 2025 is a significant -- was a year of significant revenue growth and continued financial discipline for Rigel. We'll continue to work towards the key components of our growth strategy as we look to deliver on our financial guidance for 2026.

With that, I'd like to turn the call back over to Raul. Raul?

[Raul Rodriguez, executive]

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]

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

[Joseph Pantginis, analyst]

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?

[Raul Rodriguez, executive]

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

[David Santos, executive]

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.

[Operator]

Our next question comes from Yigal Nochomovitz with Citi.

[Yigal Nochomovitz, analyst]

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?

[Raul Rodriguez, executive]

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

[Lisa Rojkjaer, executive]

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.

[Raul Rodriguez, executive]

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.

[Operator]

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

[Ashleigh Acker, analyst]

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.

[Lisa Rojkjaer, executive]

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.

[Raul Rodriguez, executive]

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.

[Operator]

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

[Farzin Haque, analyst]

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?

[Lisa Rojkjaer, executive]

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.

[Farzin Haque, analyst]

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?

[David Santos, executive]

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.

[Raul Rodriguez, executive]

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.

[Operator]

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

[Kristen Kluska, analyst]

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?

[David Santos, executive]

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.

[Operator]

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

[Raul Rodriguez, executive]

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.

[Operator]

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