Rigel Pharmaceuticals, Inc. Aktie

Greetings, and welcome to Rigel Pharmaceuticals Financial Conference Call for the Third Quarter 2026. [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.

Thank you. Welcome to our third quarter 2026 financial results conference call. The financial press release for the third quarter 2026 was issued earlier today and can be viewed along with the slides for this presentation in the News & 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 commercial, regulatory, product development and other business activities. 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 on our most recent annual report on Form 10-K for the year ended December 31, 2025, on file with the SEC and subsequent filings with the SEC, including our Q3 quarterly report on Form 10-Q 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 except as required by law.

At this time, I would 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 joining me on the call are Dave Santos, our Chief Commercial Officer; Dr. Alison Hannah, our Chief Medical Officer; and Dean Schorno, our Chief Financial Officer.

Before we begin, I'd like to share a few key highlights from the quarter. We delivered over $72 million in net product sales, our highest ever and another profitable quarter. This while making important -- taking important steps towards Rigel's next phase of growth.

Revenue, Rigel's fourth commercial product is now available in the U.S. with an encouraging start to its launch, and we continue to advance R289 towards its next stage of development. I'll start with an overview of this progress before the team takes you through the details.

Moving to Slide 4. VEPPANU became commercially available in the U.S. on August 13 and generated $6.6 million in net product sales through the end of the third quarter. Following the close of the global in-license agreement in June, our team moved quickly to initiate launch activities, leveraging our established commercial and medical infrastructure to engage physicians and build awareness ahead of commercial availability. Within just 2 months of closing the transaction, VEPPANU was successfully integrated into our existing distribution network and ready for commercial launch.

During Q3, we shipped VEPPANU to over 100 patients and clinics. Encouragingly, the majority of the patients who received VEPPANU during the early weeks of launch had already refilled their prescriptions by quarter end. We also have strong payer coverage with patients able to access VEPPANU through either formulary coverage or through the exception process.

In addition, we are seeing positive engagement with health care providers with our efforts focused on high decile prescribers. As the first and only FDA-approved PROTAC therapy, or PROteolysis Targeting Chimera, VEPPANU offers a new mechanism of action and an important treatment option for patients with ER-positive, HER2-negative ESR1 mutated advanced or metastatic breast cancer.

Our focus now is on building awareness of its differentiated mechanism and clinical data, then translating this into adoption through multifaceted campaigns. Dave will share more about our early launch experience and plans shortly.

Overall, we're excited by VEPPANU's early launch performance and believe it has the potential to be Rigel's largest sales contributor.

On Slide 5, we outline our transformational growth strategy. The VEPPANU launch is a clear example of this strategy in action. We identified a differentiated late-stage asset in oncology and leverage our established infrastructure to rapidly integrate and launch the product.

We intend to build on that approach as we continue to grow our portfolio of 4 commercial products and evaluate additional in-license opportunities. At the same time, we are investing in our development pipeline, led by R289, our dual IRAK1 and 4 inhibitor, which is currently being evaluated in the Phase 1b clinical studies in patients with lower-risk MDS. We look forward to presenting updated data on this study at the ASH meeting in December.

Financial discipline is what connects these strategic objectives. Our growing commercial business enables us to invest in opportunities with substantial long-term potential while maintaining our focus on profitability. We believe this combination of commercial execution, pipeline advancement and financial discipline sets us apart and positions Rigel well for its next phase of growth.

Slide 6 highlights our track record of commercial growth and more importantly, the opportunities ahead for Rigel. We grew our net product sales by a compound annual growth rate of approximately 35% annually since 2022.

Looking into the future, we have 2 sequential engines of significant growth: VEPPANU and then R289. We are encouraged by VEPPANU's early performance and see significant potential in the large and growing market.

Turning to R289. We continue to advance its development in patients with lower-risk MDS, a disease with significant unmet medical need. At the ASH meeting in December, we plan to present updated data from the Phase 1b study, including preliminary efficacy data from the dose expansion phase.

We also remain on track to complete enrollment and select the recommended Phase 2 dose for future development by the end of 2026. We plan to initiate a registrational program in lower-risk MDS next year and believe that R289 has the potential to be a $1 billion-plus commercial opportunity in this indication.

Together, VEPPANU and R289 offer significant commercial potential, and they are central to our plans to substantially expand Rigel's business over the coming years and drive long-term shareholder value.

With that, I'll turn the call over to Dave to discuss our commercial performance and the latest on the VEPPANU launch. Dave?

Thank you, Raul. On Slide 8, you'll see our 4 commercial products, VEPPANU, TAVALISSE, REZLIDHIA and GAVRETO.

Moving to Slide 9. Our net product sales were $72.3 million for the third quarter of 2026, an increase of 13% compared to the third quarter of 2025, primarily driven by the addition of VEPPANU during the third quarter.

And year-to-date 2026, we reported $194.2 million in net product sales, an increase of 17% compared to the same period of 2025. As Raul mentioned, we're extremely excited that VEPPANU is commercially available, and we reported $6.6 million in net product sales for the third quarter, which reflects approximately 6 weeks of product availability. I'll talk more about VEPPANU in a few minutes.

For TAVALISSE, we generated $46 million in net product sales, an increase of 3% compared to the third quarter of 2025. Eight years after launch, TAVALISSE continues to be a strong and consistent contributor to our portfolio.

For REZLIDHIA, we reported $9.9 million in net product sales, an increase of 20% compared to the prior year period. We continue to believe REZLIDHIA adoption will grow in the community setting and in the post-venetoclax patient population.

And finally, for GAVRETO, we delivered $9.8 million in net product sales, a decrease of 11% compared to the third quarter of 2025. GAVRETO continues to be a stable contributing product in our portfolio.

Overall, we are very pleased with our third quarter results. While VEPPANU is now our lead focus, we remain committed to supporting TAVALISSE, REZLIDHIA and GAVRETO. Importantly, the engagement of our field team has had around VEPPANU is opening doors to more accounts, which also creates opportunities to support our other products where there are appropriate patients.

Moving to Slide 10. We generated $8.6 million in revenues from collaborations in the third quarter, driven primarily by the availability of TAVALISSE in global markets. TAVALISSE is commercially available in key European countries under the brand name TAVLESSE in Japan and South Korea, in Canada and Israel and in Mexico through our partners, Grifols, Kissei, Medison and Knight.

Knight also announced regulatory approval of TAVALISSE in Colombia in September and the launch of TAVALISSE in Brazil in October. Our partners continue to pursue regulatory approvals for TAVALISSE in new markets, and we are pleased that access to TAVALISSE continues to spread outside the U.S.

For REZLIDHIA, our partners, Kissei and Dr. Reddy's are advancing olutasidenib in their territories.

I'll now turn to VEPPANU. Before I get into the commercial launch, let me briefly remind you of the ER-positive HER2-negative ESR1 mutated advanced or metastatic patient opportunity, which you can see on Slide 12. Of approximately 170,000 U.S. metastatic breast cancer patients, about 119,000 have ER-positive HER2-negative disease. Prior endocrine and CDK4/6 therapy drives ESR1 resistance in about 40% of patients.

Upon ctDNA testing, roughly 60%, corresponding to around 26,000 patients, are diagnosed with ESR1 mutated disease. Most of these patients are in the second or later line setting, resulting in about 20,000 patients with a critical unmet need in second line and later ER-positive HER2-negative ESR1 mutated metastatic breast cancer. This represents a U.S. market opportunity of $1 billion plus.

I'm now on Slide 13. Resistance driven by ESR1 mutations continues to be a challenge for metastatic breast cancer patients, and ER degradation is an important therapeutic strategy for addressing these mutations.

Oral SERDs degrade estrogen receptors by binding them and causing a confirmational change, which indirectly results in degradation of estrogen receptors. In a preclinical study, the scale of ER degradation was 8% to 68%. PROteolysis Targeting Chimera, or PROTAC, is not a SERD and is a very different mechanism to eliminate estrogen receptors. PROTAC is heterobifunctional, binding to the estrogen receptor on one end and the E3 ligase on the other, bringing them close together to initialize polyubiquitination, directly degrading the receptor through the proteasome.

In addition, the PROTAC can then release and degrade multiple estrogen receptors until it's metabolized. This ability to recruit the E3 ligase, remove the estrogen receptor and repeat the process differentiates PROTAC from SERD.

In a preclinical study, the PROTAC VEPPANU degraded 79% to 86% of estrogen receptors. This is why we believe VEPPANU represents an important therapeutic advance for ER-positive HER2-negative ESR1 mutated metastatic breast cancer. And as we continue to create awareness of VEPPANU as the first and only FDA-approved PROTAC, more clinicians will want to try it in their patients.

Moving to Slide 14. HCPs are interested in this new therapeutic option for their patients, and we are highly encouraged by the speed and breadth of uptake of VEPPANU during Q3. I'll be providing some metrics today to provide color on the early days of the launch, given Q3 reflects only approximately 6 weeks of availability.

Going forward, we'll not provide this level of detail given we'll be reporting net product sales. We are very pleased that immediately after product became available in mid-August, we began shipping VEPPANU to patients and clinics. In the first 6 weeks of VEPPANU availability during Q3, we shipped VEPPANU to more than 100 patients and clinics. And impressively, by the end of the quarter, the majority of patients who started in August had already received their first refill.

In terms of prescribers, we have seen both breast cancer specialists and academic institutions and community oncologists across the country try VEPPANU. In fact, all 6 of our sales regions had a prescriber on day 1 of product availability, a second prescriber by the end of week 1 and a third by the end of week 2.

Overall, to give an idea of our geographic adoption, 75% of our territories had prescribers during the first 6 weeks of product availability in Q3. Similarly, we had good adoption at direct ordering accounts across academic and community settings. All 6 regions had direct accounts ordered by the end of August and nearly 2/3 of our territories had direct account orders by the end of Q3. These early launch signals indicate that clinicians treating breast cancer have seen the value of having a new treatment option for their patients and with increased awareness and experience, VEPPANU will grow.

Moving to Slide 15. We have also been encouraged by the early trends in patient access. Prior authorization approval, or PA approval, is an important metric in determining how well a drug could be accessed.

During the third quarter, we were pleased to see that overall, our PA approval rate was estimated to be 88%. Of commercially insured patients, even at this very early stage, more than 80% of PAs were approved. And in Medicare patients, that PA approval rate was even higher, above 90%. And once patients receive approval, it is important that they get their fill quickly. And we are pleased to report that the median time to fill VEPPANU prescriptions through our specialty pharmacies was just 4 days. More than 80% of prescriptions were filled within 2 weeks and more than 1/3 of patients got their VEPPANU within 3 days.

We continue to provide services for both patients and providers through our Rigel ONECARE patient support hub. This hub can assist with benefits verification and coverage support, prior authorizations, temporary drug supply for eligible patients as well as co-pay and other assistance. These services, combined with our specialty pharmacy partners are ensuring we maximize patient access to VEPPANU and minimize the time to fill approved VEPPANU prescriptions.

Moving to Slide 16. As discussed earlier, it is important that we continue to raise awareness of VEPPANU among HCPs as the first and only FDA-approved PROTAC for their patients with ESR1 mutated metastatic breast cancer. We have made great early progress in creating awareness, and those efforts are continuing. Because VEPPANU's mechanism is so important, we have updated tools highlighting VEPPANU's novel mechanism of action and our newest promotional materials highlight a new campaign to give ER-positive HER2-negative ESR1 metastatic breast cancer patients more progression-free time to live vividly.

This is supported by our efficacy results from VERITAC-2 of a 2.4-fold increase in median PFS of 5 months for VEPPANU versus 2.1 months for fulvestrant as well as health-related quality of life patient-reported outcomes data that were reported. We are implementing plans to ensure this new promotional campaign will rapidly reach more customers as we move forward in Q4 and into 2027.

I'm on Slide 17. To that end, we will have a strong first-time presence at the most important breast cancer conference of the year, the San Antonio Breast Cancer Symposium in December. This will be Rigel's first opportunity to have a presence at this conference, and it will be strong. We have a large booth planned for the exhibit hall that prominently displays our new VEPPANU campaign.

In addition to our new HCP promotional campaign, including the newly launched website you see on the right, we will be activating numerous patient and caregiver directed VEPPANU education through several different channels.

Overall, we are highly encouraged by our early results and look forward to expanding awareness and adoption of VEPPANU as we move through our first full quarter of product availability and into 2027.

With that, I'll turn the call over to Alison for an update on our development pipeline. Alison?

Thank you, Dave.

On Slide 19, you can see our 3 hematology and oncology focus areas. R289, our dual IRAK1 and 4 inhibitor, is currently under evaluation in a Phase 1b study for patients with relapsed or refractory lower-risk MDS. And I am pleased that we will update -- present updated data from the study in an oral session at ASH in December, which will include preliminary efficacy data from the dose expansion phase of the study.

In addition, we are continuing to evaluate other potential indications for R289 where the pro-inflammatory cascade plays a role. For vepdegestrant, studies are ongoing. Pfizer and Arvinas remain responsible for these studies. I'll touch more on this in a moment.

And finally, for olutasidenib, we are focused on its evaluation through strategic collaborations with MD Anderson, the CONNECT consortium and myeloMATCH. Olutasidenib is being evaluated in IDH1 mutated AML and other hematologic malignancies as well as in IDH1 mutated high-grade glioma. You can find more information on these collaborations in our corporate presentation that's available in the Investors section of our website.

On Slide 20, you'll see more on the specific development for vepdegestrant. As I mentioned, there are several ongoing studies for which Pfizer and Arvinas remain responsible. Rigel will also contribute to these studies. These trials remain active, but are no longer enrolling except for the hepatic impairment trial.

VERITAC-2, the registrational Phase 3 study remains ongoing for time-to-event endpoints such as overall survival. In addition, there are several combination studies that we expect will provide us additional safety and efficacy data. That data will be important as we consider our future development of vepdegestrant, which includes the potential for Rigel to initiate its own studies or new collaborations.

We have heard from thought leaders that because vepdegestrant is so tolerable, it has a great potential as a combination agent. They have also told us that its differentiated mechanism of action from oral SERDs could be very important as oral SERDs are used earlier in breast cancer treatment. Thus, combination studies and studies in the post-SERD setting are of high interest and priority for vepdegestrant. Also for vepdegestrant, as Dave mentioned, we're looking forward to the upcoming San Antonio Breast Cancer Symposium.

On Slide 21 are the titles of the vepdegestrant abstracts that have been accepted, including post-SERD data and combination data and includes an abstract that discusses the impact of ESR1 mutations in the ER-positive HER2-negative metastatic breast cancer. We look forward to discussing the abstract data after the abstract embargo lifts later this month.

Now let's move on to R289 in lower-risk MDS. On Slide 23, you can see the current treatment landscape for this indication. MDS is a clonal disorder of hematopoietic stem cells that leads to ineffective hematopoiesis with consequences that include anemia, infections, iron overload and organ dysfunction and possible progression to acute myeloid leukemia. The primary goal of therapy is to reduce or eliminate transfusion dependence. In the first-line setting, patients typically receive erythropoiesis stimulating agents, or ESAs, or luspatercept. If the patient has a 5q deletion, lenalidomide is eligible.

After ESA failure or for ESA ineligible patients, luspatercept and imetelstat are approved. In the second-line setting, these treatments each have a response rate of approximately 38% to 40%, respectively.

For more aggressive disease, hypomethylating agents can be used with response rates of approximately 18% to 20%. There remains a clear need for new treatments for previously treated transfusion-dependent patients who are relapsed or refractory to or ineligible for ESAs. If the data for R289 plays out and it earns FDA approval, we see the potential for R289 to be an important therapy option for these patients.

On Slide 24, we summarize the value proposition for R289 in lower-risk MDS. There are approximately 12,200 previously treated lower-risk MDS patients in the United States and effective therapies for transfusion-dependent patients in this setting are limited. As I mentioned, R289 offers dual targeting against IRAK1 and 4. Since dysregulated inflammatory signaling in the bone marrow is associated with MDS, co-targeting of IRAK1 and 4 may suppress inflammation and LSPC function, restoring normal blood cell production.

R289 blocks toll-like receptors and IL-1 receptor signaling in vitro and has been active in preclinical models of inflammation. We established clinical proof of concept in a randomized controlled trial in healthy volunteers where R835, the active moiety of R289 markedly suppressed LPS-induced cytokine release.

The FDA has granted R289 Fast Track designation for previously treated transfusion-dependent lower-risk MDS and orphan drug designation for MDS. The preliminary Phase 1b study data presented at ASH in 2025 showed R289 had promising preliminary safety and efficacy in 33 elderly, heavily pretreated patients with relapsed or refractory lower-risk MDS.

You can see the design of our open-label multicenter Phase 1b study, evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of R289 in patients with relapsed or refractory lower-risk MDS on Slide 25.

The study is designed to select the recommended Phase 2 dose for future studies. We expect to select the dose by the end of this year. We'll then work with the FDA to align on the registrational path. We are targeting initiating a registration study in 2027.

We also plan to open exploratory cohort of the Phase 1b study, which will evaluate R289 in transfusion-dependent lower-risk MDS patients who are refractory to or ineligible for ESAs but are otherwise naive to other MDS-directed therapy. This cohort will help us understand R289's potential in earlier lines of therapy.

On the left side of Slide 26 is this year's ASH R289 abstract data that was released yesterday, which is primarily related to safety given the data of the timing cut for the submission. As of the 16th of July data cutoff, 64 patients were enrolled in the study, 33 patients in dose escalation, 31 patients in dose expansion.

The median number of prior therapies was 3 with a range of 1 to 8. Most patients were exposed to commonly used MDS-targeted agents, including ESAs, luspatercept, imetelstat, hypomethylating agents and lenalidomide. 20% had received a prior investigational agent, indicating this was a heavily pretreated population, including some with end-stage disease. These patient characteristics are consistent with the patient characteristics that were presented at ASH in 2025.

From a safety perspective, R289's profile remains consistent with what has been previously reported. Most common treatment-emergent adverse events were low-grade diarrhea, cough and dose expansion. No treatment-emergent adverse events leading to discontinuation were observed. There were no dose-limiting toxicities.

Overall, R289 continues to be well tolerated in this elderly, heavily pretreated patient population with a high baseline transfusion burden. At the meeting, updated data from the study will be presented by Dr. Garcia-Manero. The oral presentation will be included in the MDS session listed here on Saturday, December 12, and will include incremental study safety data and preliminary efficacy data from the dose expansion from a planned data cut in mid-November.

On Slide 27, I'll quickly summarize the next steps for R289. We are on track to complete enrollment and select the R289 dose for future development by the end of the year. We'll present updated data from the study at ASH in December.

Once the recommended Phase 2 dose has been selected, we will evaluate R289 in a cohort of less heavily pretreated patients who are relapsed or refractory to or ineligible for ESAs in the same study. We also plan to follow up with the FDA to discuss a potential registrational trial. Finally, we're continuing to evaluate other potential indications for R289 and plan to provide an update by the end of the year.

Lastly, on Slide 28, I want to highlight our key presentations at ASH. In addition to R289 data, we'll also have new data for fostamatinib in ITP and warm autoimmune hemolytic anemia. We are looking forward to the meeting.

With that, I'll pass the call to Dean to discuss our financial results. Dean?

Thank you, Alison. I'm on Slide 30. We reported net product sales of $72.3 million for the third quarter, a growth of 13% year-over-year, including TAVALISSE net product sales of $46 million, an increase of 3% year-over-year, GAVRETO net product sales of $9.8 million, a decrease of 11% year-over-year, REZLIDHIA net product sales of $9.9 million, an increase of 20% year-over-year and VEPPANU net product sales of $6.6 million, reflecting approximately 6 weeks of commercial availability.

Our net product sales were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance and other allowances of $21.3 million. We also reported $8.6 million of contract revenues for the third quarter, primarily consisting of $3.8 million from Grifols related to earned royalties and delivery of drug supplies, $3.2 million from Kissei related to the delivery of drug supplies and a total of $1.6 million from other parties related to delivery of drug supply and earned royalties. Our total revenues for the third quarter were $80.9 million.

Moving to Slide 31. For the third quarter of 2026, our cost of product sales was approximately $10.8 million, which includes amortization of intangible assets related to the VEPPANU transaction and royalties owed to Arvinas and Pfizer and VEPPANU net sales.

Total cost and expenses were $63.8 million compared to $41 million for the same period of 2025. The increase in cost and expenses was primarily due to higher research and development costs related to R289 and vepdegestrant clinical programs as well as higher cost of product sales, commercial-related expenses due to the commercial launch of VEPPANU and personnel-related costs.

Income before income taxes for the third quarter was $17.4 million compared to $27.6 million for the same period of 2025, and we reported net income of $13.2 million for the third quarter compared to net income of $27.9 million in the same period of 2025. We ended the quarter with cash, cash equivalents and short-term investments of $99.3 million compared to $155 million as of the end of 2025.

Turning to our financial outlook for 2026. We've updated and narrowed our guidance and now expect total revenues in the range of approximately $290 million to $295 million from the previous range of $285 million to $295 million. This includes our expectation of approximately $255 million to $260 million in net product sales, excluding VEPPANU, from the previous range of approximately $255 million to $265 million.

In addition, we now expect approximately $35 million in contract revenues from the previous expectation of approximately $30 million. We also continue to anticipate reporting positive net income for the full year while funding existing and new clinical development programs and supporting the commercial launch of VEPPANU.

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

Thank you, Dean. Turning to Slide 32. I'd like to close with a few thoughts. This is truly an exciting time at Rigel as we are successfully launching VEPPANU. We are encouraged by its strong early start and early demand.

Our commercial team is executing well, building awareness and driving adoption. Our strategy remains unchanged: grow our commercial portfolio, advance our development pipeline, evaluate potential in-license opportunities and maintain financial discipline.

2026 has been a pivotal year for Rigel. We believe the opportunities we have, particularly for VEPPANU and R289 have the potential to further transform Rigel's business and create long-term shareholder value.

With that, I'll turn the call back to the operator for your questions. Operator?

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

So 2 questions, if you don't mind. So first, for 289, curious if you could provide at least for today, it could change tomorrow, but any broad strokes about your views of a pivotal study design? What would you be looking to have the same type of randomization? I mean, I'm sorry, inclusion criteria, sizes, et cetera. Anything you'd like to share, number one?

And then number two, with regard to TAVALISSE, 8 years is a great run here, nice to still see continued growth. Any areas that you still see growth potential in the U.S. versus potential to start to hit steady state? And of course, the ex U.S. profile is still growing.

Thank you, Joe. I'll ask Alison to comment on what a registrational trial would look like. We are still working on designing such a trial. So it's a little early, but maybe she'd like to make some comments.

Thank you, Raul. So we are aware of the historical literature for this disease. There's 3 trials that were conducted in a contemporaneous manner. So this would include MEDALIST for luspatercept. It would include IMerge for imetelstat. And it would also include the failed trial called MATTERHORN. So we are aware of these trials, where they succeeded and where they came up short.

So we're taking that into consideration. As Raul mentioned, we are planning a meeting with the FDA at this time, but we're really not in a position to discuss more particulars regarding the trial design.

What we do feel comfortable saying is that next year, we fully intend to launch such a registrational trial. And as of now, early, very much on track to do so. Dave, maybe you want to comment on TAVALISSE performance?

Yes, sure. Great question, Joe. First of all, I'll say that in Q3, we did hit our highest demand bottle quarter ever in the history of the brand. So it is still growing. I think there are opportunities to grow. We can continue to get more patients out there who have ITP with our prescribers. But the real thing is, Joe, we really believe we have so much more opportunity to grow with VEPPANU. And so that's what our focus is. But that doesn't mean we don't continue to support TAVALISSE. But I think you will see sort of less growth moving forward for that brand, which will be more than made up for with the growth of VEPPANU. But I do want to recognize again that we just did again have another record demand quarter for TAVALISSE.

Our next questions come from the line of Yigal Nochomovitz with Citi.

This is Caroline y on for Yigal. Can you help us understand how much of VEPPANU's $6.6 million in sales reflected initial channel inventory stocking versus underlying patient demand? And what are October trends looking like?

Dave, do you want to take a stab at that?

Yes. Thanks for the question, Caroline. I'll say, first and foremost, the majority of the sales that we had in the first 6 weeks of the third quarter was demand related. As I said, we had a number of patients go on therapy immediately that had already refilled by the end of the quarter. We had accounts order and that speed and breadth of adoption, like I said, we were very pleased with. So I can say very firmly that the bulk of our sales were demand related as opposed to inventory stocking.

In terms of how we're doing, of course, we believe we'll continue to grow VEPPANU as we're here in the fourth quarter. And as you know, when patients start, they get refills until they progress and sometimes even beyond when they progress. So I won't make any specific comments on this quarter. You'll have to wait until next year to hear those, but we expect it to grow.

And if I may, can you tell us what the focus will be on the ASH dose expansion data for R289? Because from the abstract, it's apparent that 500 milligrams BID is the preferred dose based on PK. What else will the expansion data reveal?

So this is Alison here. I'm happy to discuss. But frankly, the presentation, we are embargoed from talking about what the slide presentation will be on the 12th of December. We provided in order to support a comparison of both doses, we provided safety. We provided pharmacokinetics, and we also provided some cytokine data. But I'm really not at liberty to go into any more specifics. I'm afraid you'll have to join us on the 12th of December when Dr. Garcia-Manero will present a more comprehensive update and really the justification for the proposed dose moving forward.

Our next questions come from the line of Farzin Haque with Jefferies.

This is James on for Farzin. Congrats on the quarter. Two from us. You lowered the upper end of guidance from $265 million to $260 million. Is there anything you're seeing in the underlying business, whether around patient starts, persistency, gross to net or seasonality that makes you more cautious on the upper end into 4Q?

And then the second question on R289 for the data at ASH, what RBCTI rate in the randomized expansion would you consider a clear success is about 40% the internal goal be? And how much follow-up will you have on durability? And what is the benchmark of transfusion independence you're trying to be?

I'll ask Dave to mention how we're doing with the commercial business, excluding VEPPANU. I think he mentioned a little bit about TAVALISSE.

Yes. Again, James, TAVALISSE hit its record demand in Q3. And I'll also say that from a REZLIDHIA perspective, you saw that we grew that year-over-year, but we also hit a record demand quarter, and it was actually 10% above -- double-digit growth above second quarter. So we are growing our business. And I think from a standpoint of our guidance, the only thing I would say is it doesn't include VEPPANU, and that is our growth driver. So I think the health of our business, though, is very strong.

Keep in mind, the demand is the most important metric underlying those products, but we also have to consider gross to net adjustments, which is driven by patient type, and it's a change in inventory is the other variable that also contribute to that.

On 289, ASH data durability?

Yes, I'm happy to comment. This is Alison here. So what we have in our Phase 1b study in the dose expansion, we have a unique population. We're very different from the population that was represented in the MEDALIST trial for luspatercept or the imetelstat trial for -- called IMerge. Those populations really have received only prior ESA, whereas if you look at the ASH abstract and you look at our priors, we have a very, very highly heavily pretreated population who have gotten not just ESAs, but nearly all patients have luspatercept, a very large number had received a hypomethylating agent. And really in the abstract, it's 29% investigational.

So talking about a true end-stage population. So we are aware of the MEDALIST data, the IMerge data. But in terms of a target for what we would think would be worthy of future studies, what we're hoping to be able to show is a very well-tolerated agent, an oral agent that's true convenience for this elderly population. I think we have a median age of 75 for our patient data set. So we don't want to come up with a target at this point. We will show the data at ASH. We did actually talk last year at ASH what our durability was. We do believe we need to have durability and a good 8-week transfusion independence to make the case to hematologists that this is a product worthy for additional investigation.

And we look forward to presenting this information.

Yes, very true.

Our next questions come from the line of Kristen Kluska with Cantor Fitzgerald.

For VEPPANU, I wanted to understand what's been the driving factor for utilization. Are these doctors with direct experience already? Or is there a factor that they've been pointing out in particular for wanting to be kind of some of the early adopters here like durability and safety?

I'm sorry, I didn't get the last part of your question, Kristen.

Yes. I wanted to know of the doctors that are using the product now if they are ones that have had direct experience from a trial perspective. But then just given that they're really kind of the first early adopters here, what has been their -- the main driving factor you hear from them about why they want to be the first to give this a chance? Is it durability, safety or another factor?

I think, first of all, we've had both. We've had clinicians who had experience in the clinical trial in one of the -- either the early Phase 1 or 2 could have been in VERITAC, could have been in later studies that were done. But by and large, the majority of clinicians who tried it have never used the product before, and they've become aware of it. And why are they interested in using it? Because it is a different kind of drug than an oral SERD.

And number two, the tolerability of the agent is something that really appeals to this patient population and to clinicians. We just posted on our website some data that came from VERITAC-2 on patient-related outcomes or patient reported outcomes in quality of life. And I think when people see the whole picture here of very good efficacy, proven efficacy for this fulvestrant and the tolerability of the agent as well as a new mechanism, they're interested in trying it.

And so I think, like I said, the best -- I always tell the team, I think, and what we're seeing is the best-selling part of this definite experience is physicians who finally try the drug because they really like it when they try it.

And then on R289, I was hoping you could further elaborate on your strategy when it comes to FDA discussions potentially next year. I guess, like how much of the open exploratory cohort data might you want to see? And how is that ultimately going to factor in how you guys are thinking about a potential registrational study?

I'm happy to comment. This is Alison. The post-ESA, what we call the exploratory cohort provides us the ability to investigate R289 in a combination of patients who have only been exposed to an ESA or for those patients in whom an ESA is not indicated, for example, they have high endogenous erythropoiesis, and there's no point in giving them an ESA. We will actually have some experience in a treatment-naive population. It's important data for us to obtain when we have our discussions with the FDA, all of the data will be brought to bear.

But I would expect that most of the data that we'll be bringing to the FDA will be from the dose escalation and the dose expansion cohorts. We will probably have very little data in that post-ESA population when we talk to the FDA.

That does not preclude from starting a clinical trial in '27. That is the plan.

Correct.

Our next questions come from the line of Allison Bratzel with Piper Sandler.

This is Peter on for Allison Bratzel. Just wondering on VEPPANU, if you can comment on the sales split between academic and community oncologists thus far? And then when might you be in a position to provide more specific revenue guidance? And then one on 289. How will the ASH data inform your evaluation of 289 and other potential indications? And any color on what those might be?

Let me ask Dave to address the first and then Alison, the second.

Yes. Our current breakdown -- and again, we'll give a little color because we are early in launch, and it's important for you guys to realize what's going on. But I'm not sure we'll be able to give these kind of specifics as we move forward. But currently, our community business is actually the overwhelming majority of our business. It's about 70% to 80% of our business if you consider HCPs who prescribe as well as accounts who order.

So it is -- it's taking off very nicely in the community, which is a little bit different than you might expect for a launch of a new agent, but it's good news for us. I think we were really happy to see that. I think we said that we should see -- we would eventually see more community business, but we're almost at the split that we've talking about before, 80%, 20%. So it is the majority community.

Dean, do you want to comment on guidance?

Yes. And with respect to guidance, as Dave said, we provided some color on some of the details during the quarter. We're just 6 weeks into our launch. As we think about guidance, we want to be in a position where we've got enough clarity of the business and the trends and trajectory. So after the first of the year, we'll consider kind of the appropriate time to provide that guidance where we believe we've got enough clarity of the business to produce a good guidance range.

And I'm happy to discuss your final question, which was how will the ASH evaluation lead to our discussions, our internal discussions regarding other potential indications. IRAK1/4, the mechanism of action really could lend itself to a variety of other diseases, including both other hematological malignancies and even potentially autoimmune disorders.

So we have these under active consideration at this time. We're not in a position to actually really prioritize where we would put the drug after we've moved it forward in low-risk MDS. But we do think the agent has really great potential, and it's not restricted to just low-risk MDS.

There are no further questions at this time. I would now like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Thank you, and thank you, everyone, for joining us today. We are very pleased with the early results of the VEPPANU launch, and we're looking forward to presenting the updated data on the Phase 1b study of R289 in low-risk MDS at the oral session on Saturday afternoon, December 12. We appreciate your continued interest and your support of Rigel. Have a good evening.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation, and enjoy the rest of your day.

This is Amin for Farzin. A couple of questions from us. First, you increased the upper bound of guidance by $5 million, which doesn't include Vepinu. The question is, what are you seeing to date for the commercial portfolio that are underpinning this assumption, and what's your expectation for the Vepinu launch this year

[p id=2 name=Raul Rodriguez type=E ]

Well, I'll ask Dave and I can comment. By the way, the change to the guidance, before I turn it over to Dave, was we increased the contract revenue from $20 million to $30 million range to approximately $30 million, as we've seen strong contract revenue come in in the first half of the year. We left intact the product sales revenue guidance of $255 million to $265 million, that sales guidance is only on TAVALISSE, GAVRETO, and REZLIDHIA. So I'll ask Dave to comment on Vepinu specifically, but we maintain our guidance on the other products.

[p id=3 name=Dave Santos type=E ]

Thanks, Raul. Yes, in terms of guidance for Vepinu, we're not going to be giving any guidance in the short term for Vepinu. Obviously, we don't have any sales yet coming in, and you'll see that after the third quarter. So we'll update you as we, you know, to give you color and insights into how the Vepinu launch is progressing. But I'll just reiterate that we believe that Vepinu is a market-leading treatment in this second-line ESR1-mutated space.

We believe we have a product with a differentiated mechanism, and it's a wholly different pharmacologic class being a heterobifunctional protein degrader and you know we have the proven efficacy that Alison reviewed, and particularly not only a very strong treatment effect in PFS, but also higher response rates both from a partial response rate or overall response rate and a clinical benefit rate, which includes stable disease, which is extremely important in metastatic breast cancer. And we think we have a tolerable agent. And for all these reasons, and frankly, even now, I think as we talk to customers, there's a lot of interest in the product. And I think the most frequent question we have is, when is the product going to be available We get this pretty much from all corners of the field. I think we're really looking forward to this product gaining traction in the.

[p id=2 name=Raul Rodriguez type=E ]

in the near future and at some point we will be issuing guidance on it. We'll have to wait a little bit until we get some time under our belt, Farzin, so that we can feel comfortable with the trajectory of the thing is. But I have to say, we're excited to see the product in the hands of clinicians and patients in short order and then providing some revenue by the end of the year, what we've accomplished this shortened year. But it's an exciting driver for us. We're happy with the performance of the other products. They're growing modestly. And this, we expect to be the real driver underlying our commercial business.

_

Thanks, that's very helpful. And just one clarification question on the Vepinu market opportunity. Can you clarify the $1 billion figure you referenced Does this represent the overall second-line ESR1-mutated opportunity available for oral SERDs, or this is an estimate specifically for Vepinu potential peak sales

[p id=3 name=Dave Santos type=E ]

That's the market opportunity. We're clear that that's, we think that the second-line and later ESR1-mutated patient population is about 20,000, which correlates to about a $1 billion market opportunity.

[p id=2 name=Raul Rodriguez type=E ]

And it's higher than that depending on what assumptions you take on pricing, etc.

[p id=-1 name=Operator ]

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

This is Jenny on Kristen's line. I have 2. While not giving any guidance on Vepinu at this time, realistically, when should we start to model in first sales and what factors should we take into consideration for cadence and penetration And then second, could you also provide some color on the ongoing studies that Pfizer is conducting, particularly those evaluating Vepinu in combination regimens

[p id=2 name=Raul Rodriguez type=E ]

Sure. So in terms of the timing, we will be reporting the Q3 sales that we accomplished, but that'll be in November. We'll actually have those. Now, this will be a shortened quarter. At J.P. Morgan, we typically put out a press release before that meeting, saying what our revenues were for the year, in which case we'll include Vepinu sales for 2026 in total. So that'll be a quarter and a little bit more than that. And at that point, we'll figure out what we're giving in terms of guidance, but we haven't decided that yet. But it may not include Vepinu at the time.

[p id=4 name=Alison Hannah type=E ]

On collaborations. Certainly, I can provide where we have been in terms of public distribution of data. The vepdegestrant plus palbociclib data was initially presented at ESMO Breast Cancer 2024. The vepdegestrant plus abemaciclib was presented at ASCO 2026. And finally, the vepdegestrant plus [ samuraciclib ] was also presented at that same meeting, ASCO 2026. The data for ribociclib and [ samuraciclib ] have not yet been publicly presented, but we would anticipate seeing those data in the future, in the not too distant future.

[p id=2 name=Raul Rodriguez type=E ]

As you know, the importance of this data is that it'll provide context for clinicians using this product in combo. As you probably heard, the product has a tolerability profile that's quite attractive and therefore may be a good partner in terms of combining with other agents.

[p id=-1 name=Operator ]

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

[p id=2 name=Raul Rodriguez type=E ]

Thank you, everyone, for joining us today. We are pleased with our second quarter performance and really look forward to Vepinu becoming commercially available later this month, in the middle of it, as well as several other important milestones with R289 that we are expected to achieve this year. We appreciate your continued interest and support and we'll keep you updated throughout the year.

[p id=-1 name=Operator ]

Thank you and have a good evening. This concludes today's teleconference. You may disconnect your line at this time. Thank you for your participation.

Greetings. Welcome to Rigel Pharmaceutical VEPPANU Licensing Agreement Conference Call. [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 conference call to discuss Rigel's in-licensing of VEPPANU or Vepdegestrant. The press release announcing the transaction was issued earlier this morning and can be viewed along with the slides for this presentation in the News and Events section of Investor Relations site on rigel.com.

As a reminder, during today's call, we may make forward-looking statements regarding our plans and timing for the regulatory review of the transaction and development and commercialization of VEPPANU. In addition, as noted in the press release issued this morning and here in the presentation, this transaction is subject to customary closing conditions, including review under the Hart-Scott-Rodino Antitrust Improvements Act. The statements made today are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks are identified in the slides and in our most recent annual report on Form 10-K for the year ended December 31, 2025, on file with the SEC and subsequent filings with the SEC, including our Q1 quarterly report on Form 10-Q 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 would 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. It's an exciting morning. Also with me today are Dave Santos, our Chief Commercial Officer; and Lisa Rojkjaer, our Chief Medical Officer. [ Thomas Lager ], our Chief Business Officer; and Dean Schorno, our Chief Financial Officer, are also here today, and they will be available during our Q&A portion of the call.

On today's call, we are excited to provide an overview of today's announcement that we are in-licensing VEPPANU for the treatment of advanced or metastatic breast cancer. Before I get to that, I am also very pleased that we have Dr. Erika Hamilton as our guest, KOL and vepdegestrant Phase III VERITAC clinical trial principal investigator on our call. Dr. Hamilton is Chief Development Officer, late phase and Director of Breast Cancer Research at the Sarah Cannon Research Institute. Thank you for being with us today, Dr. Hamilton.

Now beginning on Slide 5. I want to remind you of Rigel's transformational growth strategy in hematology and oncology. Our strategy is built upon 4 core strategic objectives: grow our commercial business, expand our portfolio through in-licensing or acquisition, advancing our clinical development pipeline and maintaining financial discipline. These four pillars are interlocking and collectively drive Rigel's long-term growth. Today, we have made a significant advance on the first two of these.

Moving on to Slide 6. We have executed on this strategy since 2020, building Rigel into the profitable company we are now. And today's transaction will help drive continued growth into the next decade. In 2020, Rigel was a single product company. Our development pipeline was limited, and we're operating in a cash deficit. Fast forward to 2025, and Rigel is a fundamentally different company. We now have 3 commercial products approved in 4 different indications. TAVALISSE was developed internally. We in-licensed REZLIDHIA in 2022 and acquired GAVRETO in 2024.

Our development pipeline is led by R289, our Rigel-discovered dual IRAK1 and 4 inhibitor, R289, is currently being evaluated in patients with lower-risk MDS. We are also in a very strong financial position, which facilitates our in-licensing strategy. Looking ahead to 2030, -- we are building on the momentum of our 3 existing commercial products, and we are continuing to advance R289 in lower-risk MDS and potentially other indications. These indications will be areas of significant unmet need and our large commercial opportunities that, again, would be transformational for Rigel.

In addition, a core focus of our growth strategy is selectively pursuing late-stage in-licensing or acquisition opportunities to further expand our commercial portfolio to enhance our growth between now and the 2030s and beyond. And I am thrilled to discuss our exclusive global licensing agreement to develop, manufacture and commercialize vepdegestrant, which has the brand name VEPPANU. Vepdegestrant or vepdeg for short, is a novel oral PROteolysis TArgeting Chimera or PROTAC. -- and on May 1 was approved by the FDA for patients with an ER-positive HER2-negative advanced or metastatic cancer with an ESR1 mutation.

There is a critical unmet need in this patient population, and we believe that VEPPANU is an important new treatment option in this setting. We are looking forward to bringing this drug to these patients.

On Slide 7, we believe that growing our commercial products, adding new in-licensed products and the advancement of our development pipeline will lead to significant revenue growth. We believe that VEPPANU will be a key contributor to our growth in the commercial portfolio and advancement of our transformational growth strategy. It has the potential to become Rigel's largest commercial product, and drive long-term revenue growth, supported by an intellectual property estate, including issued patents and potential patent extensions, which, if granted, would may extend protection through 2040 and beyond. Now let's turn to the agreement of VEPPANU.

On Slide 9, metastatic breast cancer is a major oncology market with approximately 70% of breast cancer cases being ER-positive HER2-negative, driven in part by the estrogen receptor pathway. Current standard of care in these cases is endocrine therapies. However, up to 50% of patients acquire resistance due to an ESR1 mutation following exposure to endocrine therapy, resulting in a very sizable patient population. There are about -- approximately 20,000 patients with second-line or third-line ER-positive HER2-negative ESR1 mutated metastatic breast cancer who need new treatment options to treat their disease.

This population equates to a $1 billion-plus total market opportunity in the U.S., and we believe this market will continue to grow. Before I hand the call over to Lisa to talk about VEPPANU's mechanism and differentiation, I want to share why we think this is such a compelling opportunity for Rigel.

I'm now on Slide 10. VEPPANU is the first and only approved PROteolysis TArgeting Chimera or PROTAC, a new class of targeted agent. It has a novel mechanism of action and potential to be an important new treatment option for the second and third-line ER-positive HER2-negative ESR1 mutated metastatic breast cancer. Our proven commercial and medical expertise and organization will enable us to successfully launch VEPPANU upon closing. We have successfully integrated both REZLIDHIA and GAVRETO into our portfolio, and that experience will serve us well as we integrate this new product. And we believe VEPPANU has potential to become our largest revenue producer.

On Slide 11, you will see the details of the transaction. Here are the major terms. Upon close of the transaction, Rigel will pay an upfront of $70 million to Arvinas and Pfizer. There are $15 million in near-term milestones that will be owed to Arvinas and Pfizer, which are related to the successful completion of transition activities. Additional, regulatory and commercial payments total up to $320 million, consisting of $60 million in regulatory milestones and $260 million in commercial milestones. The tiered royalties on cumulative net sales owed to Arvinas and Pfizer will range from mid-teens to mid-20s. And finally, after the close of the transaction, Pfizer will remain responsible for current ongoing development activities for vepdeg, and Rigel will contribute $40 million over the next 4 years in support.

On Slide 39, you see the various vepdeg clinical trials that are currently active. With the exception of the hepatic study, these trials are no longer enrolling. It's important to note the breadth of the studies that are being conducted. The VERITAC-2 study continues as the OS overall survival follow-up period is still ongoing.

Additionally, the various combination studies may provide key insights into additional development opportunities for vepdeg. With that, I will turn the call over to Lisa to talk about vepdeg's mechanism and differentiation. Lisa?

Thanks, Raul. On Slide 14, I will take you through the unique biology of PROteolysis TArgeting Chimera or PROTACs, which are bifunctional small molecules that destroy specific disease-causing proteins rather than just inhibiting them. PROTAC molecule consists of 3 parts: a ligand that binds to the target protein, a ligand that binds to an E3 ubiquitin ligase, which tags the target protein for breakdown and the linker connecting them.

The cell's natural waste disposal system known as the ubiquitin proteasome system recognizes the ubiquitin tag and degrades the target protein. This target tag degrade mechanism of action also freezes or releases the PROTAC to act again.

Moving to Slide 15. Vepdegestrant is the first and only FDA-approved PROTAC. It simultaneously binds the estrogen receptor or ER and an E3 ubiquitin ligase forming a complex that tags the estrogen receptor for destruction. This proteasome degrades the estrogen receptor and vepdegestrant can be reused to degrade additional estrogen receptors.

As you can see on Slide 16, the mechanism of action of PROTACs with vepdegestrant is clearly differentiated from selective estrogen receptor degraders or SERDs, such as fulvestrant. SERDs bind to the estrogen receptor, affecting the stability of or destabilizing the estrogen receptor, which makes it more prone to degradation. In contrast, PROTAC specifically target the estrogen receptor, marking it for selective destruction by the cell. This efficient and targeted ER degradation by the cell also facilitates the release of the PROTAC for further ER targeting. So conceptually, 1 SERD molecule binds estrogen receptor, while 1 PROTAC molecule can destroy many receptors, so had catalytic activity. Now I'd like to welcome Dr. Erika Hamilton. Dr. Hamilton is the Chief Development Officer, Late Phase and Director of Breast Cancer and Gynecologic Cancer Research at the Sarah Cannon Research Institute. Dr. Hamilton was the principal investigator of the Phase III VERITAC-2 clinical trial. And today, she will review the data for you. Dr. Hamilton?

Thank you so much. Appreciate you inviting me. Let's advance to Slide 18. So I'm going to walk you through the data that was presented last year at the ASCO 2025 conference, and we'll go through these slides that was the registrational trial, the VERITAC-2 study. This was looking at vepdegestrant, our PROTAC ER degrader versus fulvestrant among patients with advanced breast cancer that was ER-positive and HER2-negative. This was a global randomized study. Next slide. So our key takeaways, really, were that vepdegestrant was the first PROTAC to be evaluated in a Phase III study. It was well-tolerated and demonstrated statistically significant as well as clinically meaningful improvement in progression-free survival versus fulvestrant among patients with ESR1 mutations.

And the results of this Phase III VERITAC-2 study supported vepdegestrant as a potential treatment option for previously treated ESR1 mutation, ER-positive advanced breast cancer. Let's advance to Slide 20. So I think you've already heard some background, but essentially, there's no established consensus for treatment of ER-positive advanced breast cancer after progression on first-line endocrine therapy. Fulvestrant is a SERD that's administered intramuscularly due to poor solubility, and it has really shown that it has very limited progression-free survival benefit following progression on endocrine therapy and CDK4/6 inhibitor for our patients with PFS, really, in the 2-month or less range.

Vepdegestrant is a selective oral PROTAC ER degrader that targets wild-type as well as mutant estrogen receptor. In the first-in-human Phase I/II study, vepdegestrant was well-tolerated, and it demonstrated encouraging clinical activity in patients with heavily pre-treated ER-positive HER2-negative advanced breast cancer. We've already gone through this unique mechanism of action, but essentially directly harnessing the ubiquitin-proteasome system to degrade the estrogen receptor.

Next slide for 21. This was the design of the VERITAC-2 study. Again, it was a global Phase III trial of vepdegestrant. These were patients that were at least 18 years old, had ER-positive, HER2-negative advanced or metastatic breast cancer, and all of these patients had already received endocrine therapy in combination with a CDK4/6 inhibitor. They were permitted to receive up to 1 additional line of endocrine therapy and their most recent line of endocrine therapy, they needed to be on for at least 6 months. They were not allowed to have a prior SERD, whether that was fulvestrant or elacestrant, and they could not have had prior chemotherapy for metastatic disease.

These patients were randomized in a 1:1 fashion to either receive fulvestrant given at approved dosing, which is loading dose given intramuscularly on day 1 and day 15 and then, subsequently, every 28 days on day 1 of each cycle or vepdegestrant, which is 200 milligrams orally once daily. As you can see, over 600 patients were enrolled to the study. Our primary endpoint was progression-free survival by blinded independent central review. Initially, in those patients that had ESR1 mutations, if this was positive, then we would go on to test progression-free survival among all patients.

Secondary endpoints included overall survival, clinical benefit rate, objective response rate, as well as adverse events and tolerability. Next slide. This summarizes the statistical hypothesis testing strategy and explains how the alpha was spent. So essentially, this was a graphical gatekeeping hierarchical testing. First, we would test progression-free survival among those patients with ESR1 mutations and 3/4 of the alpha was spent here. If this was positive, then you can see we would go on to test progression-free survival in the intention-to-treat population or all patients. If this was positive, we would go on here to overall survival among patients with ESR1 mutations and then overall survival in the intention-to-treat population.

Next slide. So 624 patients were randomized, again, in a 1:1 fashion. You can see patient disposition here. The majority of patients that came off treatment did so due to progressive disease. And at the time of this data disclosure, about 20% to 30% of patients had ongoing treatment at that time. In terms of treatment duration, this was around 4 months for all patients. And you can see for the patients in the vepdegestrant arm, the treatment duration for those patients with ESR1 mutations was longer at 5.1 months and shorter at 2.8 months for those patients receiving fulvestrant.

Next slide, 24. This shows the baseline characteristics. Almost all of the patients that were treated on this study were female, about 80% of them were postmenopausal, and about 50% were Caucasian, small single digits were African-American. We did have quite a few patients that were from Asian heritage, and some patients that had an unknown or not reported race. 100% of the patients in the ESR1 mutation obviously had ESR1 mutations, but among all patients, 43% of the patients had an ESR1 mutation. This was a patient population with aggressive disease with over 60% of patients having visceral disease at baseline and about 40% of patients having liver metastases at baseline. Bone-only disease was rare, in less than 20% of our patient population.

The majority of the patients enrolled on VERITAC-2 had seen 1 prior line of therapy in the metastatic setting at around 80%, while about 20% had seen 2 prior lines of therapy in the metastatic setting. And again, highlighted in the orange box, you can see that universally, everyone had already seen a CDK4/6 inhibitor. And actually, this was pretty well-represented across CDK4/6 inhibitors. About half of patients had seen palbociclib, about 1/3 of patients had seen ribociclib, and about 20% of patients had seen abemaciclib.

Next slide. This shows the primary endpoint, which was progression-free survival by blinded independent central review among the patients with ESR1 mutations. Median progression-free survival was 5.0 months for those patients receiving vepdegestrant, where it was only 2.1 months for those patients receiving fulvestrant. This was very in line with what we expected of how fulvestrant would perform in this population. The hazard ratio was 0.57 for a statistically significant p-value of less than 0.001. You can see it's a landmark analysis of 6 months progression-free survival that more than double the percent of patients remained progression-free at 6 months that were receiving vepdegestrant compared to those patients receiving fulvestrant.

Next slide. Progression-free survival by blinded independent central review in all patients was also tested. This was 3.7 versus 3.6 months and did not meet the primary endpoint in the intention-to-treat patient population regardless of ESR1 mutation status. Next slide for Slide 27. This was investigator-assessed progression-free survival. And you can see on the left, among those patients with ESR1 mutations that, in fact, this even appeared a little bit longer with progression-free survival being 5.4 months in the vepdegestrant arm and fulvestrant 2.8 months, again, for a hazard ratio of 0.52 that was statistically significant, still with an over doubling of the number of patients that were progression-free at 6 months.

Next slide. When we look at subgroup analyses on Slide 28, we can see that the benefit of vepdegestrant extended across all populations, regardless of geographic region, whether patients were pre or postmenopausal, younger or older, whether they had presence or absence of visceral disease, liver disease, or lines of prior therapy. Next slide. For the key secondary endpoint of overall survival, this data was quite immature at the cutoff with deaths having only occurred in approximately 20% of our patients and was not able to be reported at this time.

Slide 30 shows the secondary endpoints, clinical benefit rate as well as objective response rate by blinded independent central review. On the left, you can see patients, again, that had ESR1 mutations with a clinical benefit rate of more than doubling with vepdegestrant of 42% compared to 20% with fulvestrant alone. In terms of objective response rate, this was more than a quadrupling. Only 4% of patients receiving single-agent fulvestrant had an objective response, whereas 18.6% of patients receiving vepdegestrant had an objective response.

Next slide. In terms of safety and tolerability on VERITAC-2, in Slide 31, we highlight some key findings. Grade 3 adverse events were seen in 23% of the patients receiving vepdegestrant and 18% of the patients receiving fulvestrant, which was pretty comparable. I think what really stood out to me was the AEs leading to either treatment discontinuation or dose reduction. For an investigator and somebody that's treating patients in the clinic daily, I think this is a very helpful statistic that gets at how well patients are really doing on a drug, whether they have to stop the drug, whether they have to dose reduce the drug. We saw only 3% of patients needing to discontinue vepdegestrant and only 2% of patients having to reduce the amount of vepdegestrant they were taking, leading us to conclude that this was a very well-tolerated drug among the vast majority of our patients.

On the right side of the slide, you can see the treatment-emergent adverse events that were present in at least 10% of patients in either group. Fatigue was the most common side effect, but you'll see that fatigue was still relatively infrequent. Among any grade fatigue, only 1/4 of patients receiving vepdegestrant reported any fatigue. So to say it in a different way, 3/4 of patients reported no fatigue. We also saw some increased AST-ALT in about 14% of the patients. But again, these were low grade and only 1% Grade 3, Grade 4. And notably, what you'll see on this table, 13% any grade nausea with no cases of Grade 3,4 nausea, and you do not see diarrhea on this slide because it did not meet the -- at least 10% threshold to be included in this table. Any grade diarrhea was only 6% for those patients receiving vepdegestrant. We also did do a QT interval substudy with 88 patients confirming a very mild increase of 11 milliseconds from a baseline in mean QTcF indicating that there was no large QT prolonging effect with vepdegestrant.

Next slide. So in conclusion, at ASCO last year in 2025, we concluded that vepdegestrant was the first PROTAC to be evaluated in a Phase III study, that it demonstrated statistically significant and clinically meaningful improvement in progression-free survival versus fulvestrant among patients with an ESR1 mutation in ER-positive HER2-negative advanced breast cancer. Overall survival analyses remained immature and vepdegestrant demonstrated a very favorable safety profile, evidenced by few adverse events, less than 5%, leading to either dose reduction or discontinuation among patients taking vepdegestrant. /I will now change my last bullet on this slide. As of May 1, vepdegestrant has now been FDA approved. And this certainly is an option for our patients with ESR1 mutated ER-positive HER2-negative advanced breast cancer moving forward. Thank you very much.

Thanks, Dr. Hamilton. We really appreciate you taking the time to walk us through the data and for all of your efforts to evaluate vepdegestrant in patients with advanced breast cancer. I'm on Slide 34. In summary, an unmet medical need exists for effective, well-tolerated therapies for patients with ER-positive, HER2-negative advanced breast cancer who acquire ESR1 mutations following first line endocrine therapy. Vepdegestrant is an oral PROTAC that is differentiated from other ER-targeting therapies by its mechanism of action. Vepdegestrant contains an ER ligand covalently linked to an E3 ligase, which selectively promotes proteasomal degradation of estrogen receptors.

In the pivotal Phase III VERITAC-2 trial in the population of patients whose tumors had an ESR1 mutation, a statistically significant difference in BICR-assessed PFS for vepdegestrant compared to fulvestrant was observed. Median PFS was 5 months in the vepdegestrant arm and 2.1 months in the fulvestrant arm. In addition, the incidence of treatment-emergent adverse events was low and the tolerability profile was favorable. Vepdegestrant thus has the potential to be an important treatment option in this setting. And with that, I'll hand the call over to Dave to discuss the significant unmet need. Dave?

Thank you, Lisa, and thank you, Dr. Hamilton, for the overview of VEPPANU's novel PROTAC mechanism of action and impressive clinical data from VERITAC-2. On to Slide 36. To begin, let me reiterate how excited we are with the potential of adding VEPPANU to our commercial portfolio. The slide shown here outlines the U.S. patient opportunity for ER-positive, HER2-negative ESR1 mutated advanced or metastatic breast cancer. As you can see, there are an estimated 170,000 patients in the U.S. living with metastatic breast cancer. And as Raul said, it is estimated that around 70% of those patients or 119,000 are ER-positive, HER2-negative. As we've outlined, the standard of care for these patients is to be treated with endocrine therapy and a CDK4/6 inhibitor, and exposure to these therapies over time may lead to an ESR1 mutation in up to 50% of patients. In VERITAC-2, 100% of patients had endocrine therapy and a CDK4/6 inhibitor and 43% of those patients were ESR1 mutated.

So using 40% as a benchmark, more than 47,000 estrogen receptor positive HER2-negative patients could be ESR1 mutated. Based on our internal market research, we believe about 60% of these patients are diagnosed and treated in a year. And since ESR1 mutations are acquired as exposure to endocrine therapy and CDK4/6 inhibitor treatment lengthens, the overwhelming majority of these ESR1 mutated patients are in the second line and later setting. That's how we arrive at approximately 20,000 patients diagnosed and treated each year in the second line and later setting with estrogen receptor positive, HER2-negative ESR1 mutated metastatic breast cancer in the U.S.

Breaking this down further, we believe that about 2/3 of those patients or 13,000 are in the second-line setting and 1/3 of them are approximately 7,000, are in the third line and later settings. Overall, we believe this market represents more than $1 billion in market opportunity in the U.S.

Moving to Slide 37. I wanted to provide some background on current treatments for this population of second line and later ER-positive, HER2-negative ESR1 mutated metastatic breast cancer. First and importantly, in the blue portions of the bar, you can see how oral SERDs have rapidly become the treatment of choice in the second line setting, garnering nearly 60% share since they've been introduced. Even in the third line setting, oral SERDs make up nearly 30% of treatment. This demonstrates how eager clinicians have been to find new options versus older treatments like fulvestrant, chemotherapy, or other options. And that said, those options still make up more than 40% of treatment in the second line setting and most of the treatment in the third-line setting.

The other thing you'll notice about this slide is that the use of newer oral SERDs in the second line setting is significantly higher in the academic setting, where patients are routinely tested for ESR1 mutations and awareness of new options to treat ESR1 mutated patients is high. It is important to note that while share of new agents is high in the academic setting, the overall share is much closer to that seen in the community because that is where the overwhelming majority of metastatic breast cancer is treated in the U.S. We estimate that approximately 80% of patients are treated at community oncology practices, where there is still a significant opportunity to raise awareness of new treatments for second and third line patients with ER-positive, HER2-negative ESR1 mutated metastatic breast cancer. Overall, we see significant potential for VEPPANU as a valuable new option in the treatment armamentarium for both academic and community physicians as they treat second line and later ER-positive HER2-negative ESR1 mutated metastatic breast cancer.

Moving to Slide 38. We believe that VEPPANU has the potential to become a market-leading treatment in second line and later estrogen receptor positive ESR1-mutated metastatic breast cancer. In addition to VEPPANU being the first and only approved PROTAC with a novel mechanism of action, there are 3 reasons we believe this. First of all, and most importantly, as you heard from Dr. Hamilton, VEPPANU demonstrated impressive efficacy in the Phase III VERITAC-2 study with a significant improvement in median progression-free survival. A 2.4-fold improvement or 5 months with VEPPANU versus 2.1 months with fulvestrant. Secondly, VEPPANU demonstrated tolerability in the Phase III VERITAC-2 study with a manageable safety profile and low rates and severity of GI-related events, namely vomiting and diarrhea, which can be challenging for patients on other metastatic breast cancer treatments.

Indeed, as a marker of being well tolerated, just 3% of patients discontinued VEPPANU treatment and only 2% required dose reductions. These will become important differentiators in this market. And lastly, we believe that the real-world applicability of the patient population in VERITAC-2 will be meaningful to clinicians. The standard of care for ER-positive HER2-negative metastatic breast cancer patients is use of endocrine therapy and a CDK4/6 inhibitor. VEPPANU demonstrated efficacy, safety, and tolerability in exactly this setting in VERITAC-2, where 100% of patients received a CDK4/6 inhibitor and endocrine therapy as previous treatment for their disease. Overall, we believe this combination of proven efficacy, demonstrated tolerability, and real-world applicability of the data will be compelling to clinicians as they choose treatments for second line and later ER-positive, HER2-negative ESR1 mutated metastatic breast cancer.

And finally, moving to Slide 39. VEPPANU represents a strategic addition as the fourth FDA-approved product in our portfolio. Not only does this transaction represent an opportunity to provide benefit to patients and physicians as well as a compelling commercial opportunity, but it also complements our existing commercial infrastructure and capabilities extremely well. Because we've developed significant expertise over the last 4 years, acquiring new products, smoothly transitioning them to Rigel, and rapidly having Rigel labeled product ready for patients and clinics as soon as possible after transition, we are uniquely poised to take on VEPPANU, a newly approved product that already has an NCCN listing, and make it available to patients and clinics in just a few months from now.

We have an established and highly experienced manufacturing and supply team, which will work closely with our counterparts at Pfizer and Arvinas to have product available in August or September. This team got REZLIDHIA into the channel in just 3 weeks after FDA approval and ensured GAVRETO had a seamless transition to Rigel with no interruptions in supply after the transitions. We have exactly the right expertise to bring VEPPANU to patients as soon as possible. Our commercial and medical affairs teams are already in place and experienced in focused oncology areas. We are already calling on both academic and community oncology practices. With our existing footprint in these accounts, we will be even more efficient to ensure we are able to devote our time, energy, and resources to a successful launch of VEPPANU. Further, we have developed comprehensive patient access capabilities with a track record of ensuring strong coverage and reimbursement for targeted therapies and an efficient distribution network, which can be leveraged to support commercial launch.

We will also leverage our Rigel ONECARE team with its reputation for being highly responsive to patients and providers to support a successful VEPPANU launch. Against the backdrop of our commercial and medical affairs expertise is our track record of successfully taking newly acquired assets to market quickly and efficiently, and we already have plans underway to soon begin engagement with health care providers for this important launch. We feel well-positioned to launch and rapidly grow VEPPANU into the largest brand in our portfolio.

Assuming the transaction closes in mid-June, we anticipate being well prepared to also commercially launch VEPPANU in August or September. We are tremendously excited and fully committed to bringing VEPPANU to clinicians and patients as soon as possible. Now I'll pass the call back over to Raul for closing remarks. Raul?

Thank you, Dave. The in-license of VEPPANU allows us to bring an important new therapy to patients in the U.S. with an ER-positive HER2-negative advanced or metastatic breast cancer with an ESR1 mutation, a population with significant need. VEPPANU is the first and only approved PROTAC and brings a novel and unique mechanism of action, which differentiates it from other agents. Before we go, I'd like to thank our new partners, Arvinas and Pfizer, for their dedication to bring this important new therapy to these breast cancer patients. We will take the baton from here and make sure that becomes a reality.

Slide 41. For Rigel, this is a major step forward in our transformational growth strategy, in-licensing a late-stage differentiated drug that leverages our [indiscernible] capability is exactly what we have been working towards. Upon deal closing, VEPPANU has the potential to be Rigel's largest commercial drug, and we anticipate this deal to be accretive. This will allow Rigel to generate additional cash in future years, allowing us to invest more in our pipeline to create additional and larger transformational opportunities in the near future. With that, operator, we are ready to take questions.

[Operator Instructions] Our first question is from Joe Pantginis with H.C. Wainwright.

Very exciting transaction. So 2 questions, please. So first for Dr. Hamilton. So just curious now with this newly approved drug, what do you consider the important next steps? Of course, education is number one with regard to the readiness of physicians to include VEPPANU into the Rx pipeline [ with these ] physicians.

Yes, I think that's a great question. I think physicians are used to having options in the second line. And luckily, we are also used to having to test for ESR1. That's not a new paradigm for us having 2 other therapeutics that are linked to an ESR1 mutation. So I think there is the advantage that, that is already becoming quite routine in clinical practice. I think the selling point of vepdegestrant is really going to be the adverse event profile. I think SERDs in general are a pretty well-tolerated compound group.

But if we had to pick something that we don't love about them, it's probably GI toxicity. And that varies from compound to compound, but pretty much all of them in the class have a little bit of problems with nausea, diarrhea, that type of GI toxicity. And I think that's really where vepdegestrant in the clinical trial, and obviously, through the AE table appears really clean. And I think that's going to be a differentiator for clinicians and patients.

And then for the company, if I can fast forward a little bit, obviously, you're taking on the global rights as well. And can you discuss whether Arvinas and Pfizer have been in any ex U.S. discussions? And will you be taking over those discussions if they have been in progress?

I can answer that. This is Raul. We do have global rights for this product, and there are opportunities for this product given its unique mechanism and the data supporting its approval, both AE and certainly from a GI, as Dr. Hamilton just said. And so I think there's opportunities outside of the U.S. as well. And much like we did with our REZLIDHIA product, we will look for partners outside the U.S. and evaluate those in and in sequence, put them in place. Our colleagues at Pfizer were really looking for a global deal. /And so they really haven't looked into separating this out as yet. So we will begin that process at the right moment and hopefully be successful in putting partnerships in place. We have with all our prior products where we had ex U.S. rights. So I have no doubt we'll succeed in that as well.

Our next question is from Kristen Kluska with Cantor Fitzgerald.

Congrats on this deal. So you made -- you mentioned a couple of times that this product has the potential to be your highest selling product. I'm curious if that includes commentary based on where the approval is today or if that factors in potential indications. And I know that your partners have some studies ongoing right now, which they're responsible for. But does Rigel intend to launch any potential studies in other indications -- settings, excuse me?

Yes. I can answer that, and Lisa would contribute that, to a degree. We think this has potential to be our largest product with the current label. I think it's an exciting opportunity for us. It's the basis why we were excited to enter discussions about acquiring this product. It's a really great fit, as Dave just said, with what we are capable of doing. So our ability to effect -- commercialize this product effectively, communicate to the doctor community is, I think, quite good, and we're able to make this product a successful launch in a market that's quite sizable, over $1 billion market. So we're -- we think that it has tremendous opportunity here. Also some opportunities outside, beyond this, but those are still a bit early, and we will return out to you and say, "Here's other things we might be able to do with it." Lisa, any commentary?

Yes. I think -- thanks, Raul. I think that as you saw on the table with some of the trials that are wrapping up, there is still some data coming that we think will be useful to clinicians and specifically regarding combinations. And I think we're going to wait and see the final results of those studies and make some future decisions.

And can you comment a little bit about the internal work you're going to do to prepare for launch, what a sales for this might look like? It seems like with the oral SERD that the interest in uptake was quite rapid out of the gate. So I'm wondering how much of that really needs to be driven by the Rigel team really getting their foot in the door and pounding the table versus the market just, frankly, being aware of everything going on in the space as well.

Dave, maybe you could comment on that?

First of all, thanks for the question. We have been doing diligence on this for quite a while. A number of my commercial and medical affairs colleagues have been really looking at this, and we view this as an outstanding opportunity. So we do believe it will become our largest product in our portfolio with the current indication, just to reiterate what Raul said. And yes, there is a tremendous enthusiasm among clinicians to find new options for treating their metastatic breast cancer patients, and it is evidenced by the fact that adoption of the oral SERDs has been quite rapid.

And so we think that's great because I think they'll be open to a drug that has a proven efficacy profile as well as an outstanding tolerability profile. /And as Dr. Hamilton has reiterated, that 3% discontinuation rate and 2% of dose reduction rate is -- makes it pretty clear to clinicians that this is a drug that patients will take. And we will really message that efficacy that you have, but without any trade-offs in terms of your patients being able to take this. And that's a key, not to mention that we have the first and only PROTAC as well -- that's approved, which is, I think, a new wave of heterobifunctional protein degraders that are coming as well as that novel mechanism of action. And so these are the differentiators that we can have. And we think we can do that with pretty much our current team. /Realize that we are calling on most community practices here in the U.S. with TAVALISSE. TAVALISSE is widely used across most oncology practices. And with REZLIDHIA, we have outstanding experience in institutions with our institutional team.

We do anticipate small increases to make sure we can cover both REZLIDHIA and VEPPANU in the institutions, but we really don't see a major increase in our sales force size. And our team, I can tell you, I have tremendous confidence in our team. They are terrific at getting the word out there, and I know they're going to be tremendously excited about this opportunity.

So we've got a great product, and we have a terrific team, and I think we're going to execute just like we've always done to grow our products. And I think we can continue to do what we've been doing with our current product line, but this becomes the focus. This becomes the energizer for our entire team. And I'm telling you, I really do think we can accelerate uptake and have this become our largest product in our portfolio.

Our next question is from Yigal Nochomovitz with Citi.

Congrats on this transaction. You sort of answered it a little bit already, but Raul, I'm wondering if you could expand a little bit on the strategy. Obviously, you've had a strong confidence in heme with the existing portfolio. Could you just talk a little bit about more about how you become comfortable moving into solid tumors with this transaction? /And then for the doctor, if you could speak a little bit more about the competitive landscape with some of the other agents that are going to follow the Phase III data, I believe, later in the year, palazestrant being one of them. Just curious if you could comment on how you see vepdeg fitting into that landscape?

Thanks, Yigal. Let me answer the first one, and then I'll ask Dr. Hamilton to answer the question on competitive agents in the area. We initiated our entry into the solid tumor market with the acquisition of GAVRETO. So that was our first solid tumor product. And part of the rationale for that is that we looked at our sales force, and they had substantial solid tumor experience and relationships with doctors in a variety of different areas. So this solid tumors are not an area that's new to our sales capability at all. And we built some very good relationships based on GAVRETO. And in many ways, this allowed us to take on this opportunity. It's an opportunity that's substantially larger and 1 where I think we have a drug here that could be really a great addition to the armamentarium in the second and third line breast cancer market. And I think we're well prepared to do it.

As Dave said, our team has evaluated this product for many months as we did diligence, primary market research, began studying what doctors we need to address in this in preparation for a potential launch. So I think we're in great shape for launching this product in the near future, and I think making it a success and really proud to have been selected by Arvinas and Pfizer. They did a great job in taking the product to this point. And now, I think, we're the ideal commercial partner for them because of what we know about the solid tumor area. And with really fairly small number of ads, we'll be able to commercialize quite effectively. Dr. Hamilton, the question on other competitive agents in this space, maybe you can comment on those?

Yes. I mean, I think, I kind of already alluded to the fact that second, third line ER-positive breast cancer is tricky because it's a complicated space. We used to just have fulvestrant and now we're profiling. We're looking for PI3, AKT, PTEN alterations. We're looking for ESR1 mutations. And then we're also trying to find something to do with patients that don't have a mutation. So really, the competitive landscape for patients that have an ESR1 mutation right now.

We have 2 other FDA-approved agents, elacestrant and imlunestrant. Elacestrant was kind of first to the party. It's not -- it's called a SERD. It's not -- technically, it's SERD activity isn't quite as high as its SERM activity for a lot of us that really understand that compound. I think its benefit has really been when we select for patients that have really benefited on prior endocrine therapy for a very long time. Imlunestrant, it's a little bit hard to compare the imlunestrant data to elacestrant or vepdegestrant because unlike those 2 trials, in the imlunestrant trial, the patients had not all seen CDK4/6 inhibitor. So when you kind of do the dreaded cross-trial comparison, you'll note that progression-free survival is longer in the imlunestrant trial.

But in fact, the control arm did doubly as well in the imlunestrant trial. So really not comparing apples-to-apples. Again, I mean, I think the oral SERDs have a little bit more GI toxicity, in my opinion, than vepdegestrant does. Ultimately, I think that gets back to patient tolerability and how they feel day-to-day on an oral therapy that they're taking at home and also in the future to combinability with other agents.

The other option patients have is to do something that isn't a single agent, combining fulvestrant with an abemaciclib or other combinations like an everolimus. Although those regimens can be efficacious, whenever we do combinations, we add toxicity. And so really, we kind of discussed that with our patients, but a lot of patients really wanting to pick what they're going to feel well on and have the best quality of life on. And I think that's really where single agent shine.

Okay. And just one quick one for the company. You mentioned $60 million in additional regulatory milestones. I gather that's for other territories outside of the United States. Can you just clarify, please?

Our next question is from Farzin Haque with Jefferies.

Congrats on the deal. Maybe one question for Dr. Hamilton, following up on the last response. Like from an uptake perspective in the real world use, like use of chemo and then the increasing use of SERDs that you mentioned. So in what patient setting would you prescribe VEPPANU, like primarily in new second line patients? Or will you use it also for patients progressing on the ORSERDU and Inluriyo? And also the SERD chemo, for example, these patients were not part of the clinical design that you mentioned. So any color would help.

Yes, I'll try to answer that. I think whether we're talking about chemotherapy or antibody drug conjugates, those drugs should really be reserved for patients when they're no longer appropriate for endocrine therapy. We really should be exhausting our endocrine agents before we move on to those agents. So that's somebody that didn't get benefit from their last line of endocrine therapy and is no longer appropriate to receive more endocrine therapy. We're typically not going to give chemotherapy and come back to an endocrine therapy, again, if we've been systematic and used our endocrine therapies appropriately before we've moved on to chemotherapy. Does that answer your question there?

Yes, that makes it clear. And then for the management team, like following the -- there's a term loan for $45 million that you retired and then you had that. So how are you going to fund the $70 million? Is it through the existing cash reserve or through the drawdown of the new $40 million revolving credit?

Thanks for that. I'll ask Dean to address that. Dean? An issue. Let me address that. We ended the quarter with about $146 million in cash. So it's a very good cash position. We're planning on using that cash to fund this, to be a comfortable number for us. And in addition to that, beyond that, if we choose to, we do have a credit facility that we could tap into with MidCap as we announced a week ago. We restructured that facility to an AR credit line and drew down $8 million for that. So we still have ample capacity there as well. So the combination of the 2 puts us in a very strong position to do the trial -- this license.

Our final question is from Allison Bratzel with Piper Sandler.

This is Ashleigh on for Alli. Congrats on the transaction. Just one question from us. I was just curious to get your thoughts and also hear Dr. Hamilton chime in. With the label requiring an FDA-authorized test for ESR1 mutations, what's the strategy for ensuring broad access to diagnostic testing to facilitate rapid patient identification and uptake? And maybe, Dr. Hamilton, you can expand more on the [ docs ] experience of this. I know there's information in the label itself on FDA-authorized detection test, but any color around this would be helpful.

Dr. Hamilton?

Yes. So this is -- the label saying an FDA-authorized test is really just alluding to the fact that patients need to have an ESR1 mutation. So they're not specifying that you have to have that in a certain brand of test, but this is really any commercially available test. And so we have a variety of those available, whether we're talking about tissue-based testing or whether we're also talking about blood-based or liquid biopsies. So there's multiple vendors that supply those.

This is Dave. I'll also comment that, as I said, we've done a lot of market research in this area. And as I said on my prepared remarks, testing in the academic institutions is very, very high and nearly universal. In the community, it's still pretty high in breast cancer and particularly because this is a ctDNA test that's commercially available, and they also have a team that goes out and talks to them about this test.

So it is being done in a majority of community practices. So we don't see testing as necessarily an area that we will focus on and increase the testing rate. We think that's going to grow organically in the community practices. We'll continue to talk about revenue there, but we do expect that testing, especially for ESR1 in metastatic breast cancer will become more prevalent in the community as time moves on.

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

Thank you very much, operator, and thank you for your questions. And thank you very much, Dr. Hamilton. We appreciate your insight and your contributions to this drug. It's really an incredible advance in terms of providing this drug to breast cancer patients. We look forward to taking that step and executing on that in the near future. It's an exciting moment for the company as well as we take the next step in adding to our portfolio, utilizing, leveraging our commercial organization and increasing the sales base of the company nicely with this transaction. So with that, I'd like to thank you for your interest and your participation on this call. Have a good day.

Thank you. This does conclude today's teleconference. You may disconnect your lines at this time, and thank you for your participation.

Greetings, and welcome to Rigel Pharmaceuticals Financial Conference call for the first quarter 2026. At this time, all participants are in a listen-only moment. A brief question-and-answer session will file the formal presentation. If anyone should require. As a reminder, this conference is being recorded. It is now my pleasure to introduce our speaker, Ray Furey, Rigel's Executive Vice President, General Counsel and Corporate Secretary. Thank you. Mr. Furey, you may begin.

Welcome to our first quarter 2026 financial results and business update conference call. The financial press release for the first quarter 2026 was issued a short while ago and can be viewed in a granite slides for this presentation in the News & 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 regulatory 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 Form 10-K for the year ended December 31 and 2025 on file with the SEC and subsequent filings with the SEC including the Q1 quarterly report on Form 10-Q 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.

Rick, and thank you for joining us today. Also joining me on the call today are Dave Santos, our Chief Commercial Officer; [indiscernible] our Chief Medical Officer; and Dean Schorno, our Chief Financial Officer. Beginning on Slide 4.

I will review our first quarter performance, outline Rigel's growth strategy and highlight the key strategic initiatives that position us for continued growth. Rigel is in a solid position with a growing product portfolio a solid financial foundation in an advancing clinical pipeline. In the first quarter of 2026, we generated net product sales of just under $55 million, representing a 26% growth.

Compared to the first quarter of 2025. As expected, the first quarter was impacted by seasonal factors, including reimbursement dynamics patterns we have seen historically at within our business and across our industry. Encouragingly, we saw -- we observed improving demand in March. Similar to prior years, we expect to return to sequential growth starting in the second quarter driven by improving demand trends. .

As a result, we are maintaining our 2026 revenue guidance for total revenues of $275 million to $290 million, including net product sales of $255 million to $265 million. We also remain on track to achieve net income profitability in 2026, and we will continue to update you on our progress throughout the year. .

We're also very encouraged by the continued progress of our R 289 program in lower-risk MDS with data expected by year-end. In parallel, we are actively evaluating late-stage in-license or acquisition opportunities that would support potential launches between 2026 and 2028.

Now looking turn to our transformational growth strategy. This strategy is guided -- has added Rigel's evolution. It is built on 4 core strategic objectives. Continued commercial execution, pipeline expansion through in-licensing or acquisition of late-stage assets, advancing our clinical development pipeline and maintaining financial discipline.

These 4 pillars form the combination of Rigel's growth strategy. Today, I will walk you through how we have successfully executed this strategy since 2020 to build the company we are today and how we plan to continue driving growth going forward.

Moving to Slide 5. Back in 2020, Rigel was a single product company with a limited development pipeline and negative operating cash flows. Today, as we look at our progress through 2025 and towards 2030, we are fundamentally a different open.

We now have 3 commercial products, [ Tavares, Breloer and GAVRETO ] approved across 4 indications. 289 is advancing in lower-risk MDS, and this program has the potential to expand into large markets with significant unmet medical need. Importantly, we achieved profitability in the third quarter of 2024, and through the end of 2025, we generated over $100 million in cash, reflecting our financial discipline.

We are operating from a position of financial strength allowing us to fund our operations and continue advancing and expanding our pipeline. Moving to Slide 6. Since emerging from the [ Kometan ] even, we have delivered strong net product sales growth driven by solid commercial execution and successful portfolio expansion. And we believe this is just the beginning.

We see multiple opportunities for us to drive another phase of transformational revenue growth horizon. In addition to growth of our current products, we are also focusing on adding new assets through in-licensing or product acquisition as well as advancing our internal pipeline, particularly Art Ignite and lower-risk MDS and other potential indications.

These programs potentially represent significant long-term opportunities that could expand our commercial portfolio in the 2030s and beyond, supporting sustained growth and long-term shareholder value. Before I hand the call over to Dave to review our commercial performance, let me briefly remind you of our approach to in-licensing and business development. On Slide 8.

You'll see that we're targeting differentiated assets in hematology, oncology and related areas. You've seen us successfully integrate [indiscernible] into our portfolio in 2022 and 2024, respectively. Today, we are pursuing similar opportunities, potentially larger in scale given Rigel's growth since those earlier transactions.

We are focused on late-stage assets with potential commercial launches in the next 3 years. By late stage, we mean assets that are NDA ready for filing or are already under review or are already approved. Importantly, we prioritize opportunities where we can leverage our existing infrastructure to drive operational efficiencies and accelerate revenue contribution and generate cash. With that, I'll turn the call over to Dave. Dave?

Thank you, Raul. On Slide 10, you'll see our 3 commercial products Top lease, GAVRETO and Risley. Moving to Slide 11. We are pleased with the year-over-year growth in revenues for the first quarter continuing our trend of growing each quarter's sales over the previous year as evidenced by this slide.

In the first quarter of 2026, we generated $54.9 million in U.S. net product sales. an increase of $11.3 million over Q1 of 2025, representing a 26% increase year-over-year. Our first quarter net sales were impacted by typical first water reimbursement dynamics, such as resetting of deductibles, co-pays and other access delays for Medicare patients with plan changes that took effect in January.

Consistent with this pattern, our first quarter 2026 net product sales reflected the impact of these seasonal factors, which primarily affected January and February orders. We observed improving demand in March, which showed stronger volume across our product portfolio. Specifically on [ TAVALISSE ] I'm pleased to report another strong quarter in which we generated $37.3 million in net product sales, an increase of 31% compared to the first quarter of 2025.

This growth was driven by both stronger demand and a favorable gross to net versus last year. As a reminder, in 2025, we experienced a onetime influx of patients due to the elimination of the coverage gap and improved affordability for Medicare patients.

For [indiscernible] we delivered $9.6 million in net product sales, an increase of 7% and compared to the first quarter of 2025. GAVRETO has become a stable, contributing product in our portfolio. And for relet, we reported $8 million in net product sales. an increase of 31% compared to the prior year period.

We saw a continued building of breadth and depth in academic accounts and remain focused on growing use in the community. With new venetoclax-based therapy data showing superiority to intensive therapy in the frontline setting. We expect that reside as consistent efficacy in the post venetoclax setting to become even more relevant and improve adoption in the community.

Overall, we have begun 2026 with significant 26% growth versus Q1 of 2025. And with our continued focus on TAVALISSE patient starts and improved adoption of [indiscernible] particularly in the community, our commercial team looks forward to driving continued momentum for our products in 2026. My sincere thanks to the entire team for all their hard work.

Moving to Slide 12. We generated $3.9 million in revenues from collaborations in the first quarter driven by the availability of TAVALISSE in global markets. TAVALISSE is commercially available in Europe under the brand name Cables. In Japan and South Korea and Asia, and in Canada and Israel via our partners, Cripples, Kissei and Madison.

In addition, our partners continue to pursue regulatory approvals for TAVI in new markets. And we continue to work on expanding access to our products in markets outside of the U.S. for Reliva in 2024 and 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 resilo in preparation for future potentially potential regulatory sufficient. We are pleased that access to our products is expanding outside the U.S. And with that, I'll now pass the call over to Lisa to provide an update on our development pipeline. Lisa?

Thanks, Dave. I'll now provide an update on our progress over the first quarter and plans for the remainder of the year. Have on Slide 14. Our hematology and oncology pipeline focus is the clinical development of R289, our potent and selective dual IRAK1 and IRAK4 inhibitor in lower-risk pilospostic syndrome or MDS, and the expansion of elutucitinib beyond relapsed or refractory IDH1 AML in collaboration with academic partners. .

Our Phase Ib study of R-289 in patients with relapsed or refractory lower-risk MDS is progressing well. Shortly, I'll provide an update on the study as well as our planned next steps for R289. As far as the itacitinib development is considered, our strategic collaborations continue to invest into additional therapeutic areas.

MD Anderson is evaluating olutasidenib and several IDH1 mutation positive indications, including AML, MDS and CMML. In addition, olutasidenib is also being evaluated as a maintenance therapy and as a co-targeted therapy in AML. The 5 and the Anderson studies are active and enrolling.

Connect Phase II TARGET B study evaluating olutasidenib with a combination with temozolomide followed by olutasidenib therapy as maintenance treatment and newly diagnosed pediatric and young adult patients with IDH1 mutation positive high-grade glioma is also active and enrolling patients.

Lastly, we're partnering with the National Institutes of Health and National Cancer Institute, isolate precision medicine trial initiative. The planned study will evaluate olutasidenib first-line IDH1 mutated AML and MDS.

We're excited about olutasidenib 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 will discuss R-289, our novel dual IRAK1 and IRAK4 inhibitor.

I'm on Slide 16. We I'd like to remind you about the treatment landscape for lower-risk MDS. MDS is a clonal disorder of hematopoietic stem cells, leading to deflation and an effective hitopolesis. The main consequences for patients are anemia and transfusion dependence, which adversely impact their quality of life.

In addition, sections iron overload from transfusions and subsequent organ dysfunction all negatively impact the patients. Therapies used in the upfront setting include erythropoiesis-stimulating agents, or ESAs, the patients are eligible for luspatercept.

Luspatercept and the metal stat 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 the metals there is still a need for safe effective therapies for previously treated transfusion-dependent, lower-risk MDS patients that are relapsed refractory to or ineligible for ESAs.

On Slide 17 is the value proposition of R289 in lower-risk MDS, which we believe can address beyond that need, particularly for transfusion-dependent patients. There are about 12,000 previously treated lower-risk MDS patients in the U.S. that could benefit from a novel therapy like R-289. This regulation of inflammatory signaling is key to the pathogenesis of lower-risk MDS.

IRAK-1 and 4 mediate this process. blocking both IRAK-1 and 4 may suppress marrow inflammation and leukemic stem and progenitor cell function and restore normal hematopoesis. R-835 the active [indiscernible] block 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 as inflammatory effects came from a healthy volunteer study in which R-835 markedly suppressed LPS-induced cytokine release compared to placebo. As a reminder, R-289, which is currently being evaluated in the clinic is the oral prodrug that is rapidly converted to R835 in the best.

From the FDA, R-289 has both fast track designation for the treatment of patients with previously treated transfusion-dependent lower risk MDS and orphan drug designation for MDS.

Both designations underscore the agency's interest in this rare disease, the unmet need of the patient population and the agency's willingness to collaborate with Rigel in the development of R-289 has thus far demonstrated a promising clinical profile with both encouraging preliminary safety and efficacy in our Phase Ib study, which was presented at ASH this past December.

Now on Slide 18, you can see the design of our multicenter open-label Phase Ib study in patients with relapsed/refractory lower-risk MDS, the Phase Ib study evaluates the safety, tolerability, PK or pharmacokinetics and preliminary efficacy of R-289 in patients with lower risk MDS and is also designed to select the dose for future studies. The dose escalation phase evaluated 6 different R-289 dosing regimens that are administered once or twice daily using a modified 3+3 design.

And the dose expansion part of the study, which is currently enrolling up to 40 transfusion-dependent relapsed/refractory lower-risk MDS patients are being randomized to receive R-289 doses of either 500 milligrams once or twice daily in order to select the recommended Phase II dose for future clinical studies.

On Slide 19, you'll see highlights from the dose escalation phase data that were presented at the ASH meeting in December. I encourage you to review the corporate presentation on the Investors section of our website, which includes the full data set. 33 patients were enrolled. The median age was 75% and the median number of prior therapies was 3 with around 70% of the patients having received prior luspatercept and HMAs.

In addition, the majority of the patients had a high baseline transfusion burden. This elderly, heavily pretreated patient population is truly representative of the lower MDS patient population with the highest unmet medical need. Overall, R-289 was generally well tolerated with a low incidence of Grade 3 or 4 cytopenias and infections.

There was 1 dose-limiting toxicity reported a Grade 3 AST/ALT increase of 750-milligram daily dose level and no evidence of dose-dependent toxicity across the other dose groups. The solar plot you see 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 16 weeks prior to start of R-289 are shown to the left of the colored bars -- establishing the baseline transfusion frequency for each patient of 18 evaluable patients receiving doses of 500 milligrams daily or higher, 6 patients or 33% achieved red cell transfusion independence or RBCTI lasting for 8 weeks or longer.

In 4 patients, RBCTI lasted for more than 16 weeks and for 3 patients for more than 6 months. The median duration of RBCTI was around 23 weeks, ranging from 9 weeks to more than 24 months. Also, the median time to onset of RBCTI was about 2 months.

While this is a small data set, we're encouraged by these results given the highly refractory nature of these patients. In summary, R-289 was generally well tolerated with an encouraging safety profile and promising preliminary efficacy in an [indiscernible] heavily pretreated transfusion-dependent lower-risk MDS patient population.

The next steps for our R-289 clinical development program are on Slide 20. We plan to complete enrollment of the dose expansion phase of the study and select the recommended Phase II dose for future studies in the second half of this year.

We anticipate sharing an update on the study, including top line data from the dose expansion phase by the end of 2026. Once the recommended Phase II dose has been selective, we will evaluate R-289 in the cohort of less heavily pretreated patients who are relapsed refractory to or ineligible for ESAs in the same study.

Upon completion of the Phase Ib study, we plan to follow up with the FDA to discuss the potential registration study, which will potentially initiate in 2027. With its mechanism of action, we believe that R-289 has potential in other indications where the pro-inflammatory [indiscernible] plays a role, and we'll provide more details as our plans progress.

Now I'll pass the call to Dean to discuss our results for the quarter. Dean?

Thank you, Lisa. I'm on Slide 22, we reported net product sales of $54.9 million for the first quarter growth of 26% year-over-year, including TAVALISSE net product sales of $37.3 million, a growth of 31% year-over-year have better net product sales of $9.6 million, a growth of 7% year-over-year.

Lastly, we reported [indiscernible] net product sales of $8 million, a growth of 31% year-over-year. Our net product sales were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance and other allowances of $20.5 million.

We also reported $3.9 million of contract revenues for the first quarter primarily consisting of $1.8 million of revenue from Grifols related to earn royalties, $1.8 million of revenues from [indiscernible] related to delivery of drug supplies and $300,000 of revenue from Medison related to delivery of drug supply and earned royalties.

This brings our total revenue for the first quarter to $58.8 million. Moving to Slide 23. For the first quarter of 2026, our cost of product sales was approximately $4.6 million.

Total cost and expenses were $46.9 million compared to $40.6 million for the same period of 2025. The increase in cost and expenses was primarily due to increased research and development costs, driven by the timing of clinical activities related to R-289 as well as increased commercial-related expenses and personnel-related costs. Income before income taxes was $11.7 million.

We reported net income of $8.7 million for the first quarter compared to net income of $11.4 million in the same period in 2020. We ended the quarter with cash, pass equivalents and short-term investments of $146.7 million compared to $155 million as of the end of 2025. Turning to our financial outlook for 2026.

We continue to expect total revenue in the range of approximately $275 million to $290 million. This includes our expectation 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 opportunities.

Before I turn the call back over to Raul, I'd like to also describe 2 recent updates. In mid-April, we received notification from Lilly that they will terminate the collaboration with Rigel which included the development of olutasidenib. Previously, R-552. The RIPK1 asset was being evaluated in a Phase II study in adult patients with moderately to severely active rheumatoid arthritis.

The termination will become effective on June 15, 2026. As a reminder, the CNS portion of collaboration was previously terminated in November of 2025. We expect to regain rights to the program upon termination.

But let me remind you that our revenue guidance does not include any assumed revenues from Loy collaboration. In addition, the termination does not impact our ability to finance our operations.

Finally, earlier today, we restructured our debt agreement with MidCap Financial to replace our existing term loan credit facility with a revolving credit facility. Roger repaid the remaining outstanding term loan balance of $40 million and now has a revolving credit facility for $40 million with an option to increase it to $60 million, subject to customary conditions.

We've drawn down $8 million on the new revolving credit facility. We believe this agreement provides us with a cost-efficient source of flexible finance into the future. And with that, I'd like to turn the call back over to Raul.

Thank you, Dean. Moving to Slide 24. To wrap up, our key priorities for the remainder of 2026 are clear, continue to grow our commercial business, pursuing license opportunities to further expand our portfolio. Advance our development pipeline with a focus on R-289 in lower-risk MDS and potentially other indications and maintain financial discipline as we work to deliver yet another year of top line growth and positive net income.

We are proud of the transformational growth that Rides achieved over the past several years. We are excited to continue executing on our 4 strategic objectives to drive long-term value creation in the years ahead. With that, I would like to turn the call over to your questions. And operator, we are ready.

[Operator Instructions] Our first question comes from the line of Yigal Nochomovitz Citigroup. Please proceed with your question.

This is Carly on for Ygal. Congrats on the quarter. Can you please talk about your plans for the RIPK1 inhibitor now and maybe comment on the y fashion for terminating the agreement .

Sure. Thank you. I could answer that question. And thank you for asking that because it gives me a chance to thank our colleagues at Lilly for the collaborative spirit and diligence that they showed throughout our collaboration. .

We put the collar, let me though in the framework of what Rigel is and how it fits within Rigel. Roger is a hematology oncology-focused company. We have a growing commercial business. We are profitable. and we have a pipeline in hematology oncology with tremendous opportunities.

We did this deal with kinase with [ Willi ] because the primary focus of kinase is in immunology and CNS diseases.

And those who we felt were best suited to a larger pharma company like Lilly that are interested in those areas and the resources to explore the opportunity there. For us, though it was really a financial upside that this provided and really not a strategic focus of ours.

So it tuned as well in terms of having a partnership, that was the rationale. Now getting in fact, I think we will assess what to do as a next step. It's not a key focus of this company, and we'll decide what we do as a next step going forward in the near future.

But again, thank you for the partnership and our colleagues, I believe, over these years.

Our next question comes from the line of Joe Pantginis with HC Wainright.

So first, I just wanted to check on your [ Lidya ] comment. Obviously, the blocking and tackling continues with the academic centers. But with regard to growing community centers, obviously, it's educating them in the post-event setting, as you described.

Are there any other drivers or key factors that are I don't want to call it rate limiting steps, but things that you feel need additional work.

I think you've got it there. Joe, this is Dave, by the way, sorry. I just wanted to reiterate the post-end setting is really important to community clinicians because that is their standard of care in the frontline setting.

And so helping them to become aware of our data in the [indiscernible] setting is compelling to them. So that's number one. I do think in terms of challenges in the community, you'll have to recognize that community physicians do not treat AML every day.

And in fact, they don't see IDH1 mutated AML very often. -- into -- and all, even less than the AML because IDH1 is a subset of that. And so for a habit is to go to something they know.

And as you know, the other agents in the class has been out for a long time. And so it is a force of habit that we need to overcome. And the key is getting the right message to them at the right time.

And that's when they have an IDH1 patient and that's what we've spent a lot of time trying to figure out how do we help our field team get to accounts, community accounts in particular at the right time with that message.

And we've done a lot of work around that. not only using diagnostic data, but even like coming through medical data, patient journey data to really understand when that patient may occur. So that's what we provide our field with. That's what they target with, and that's when they go and deliver the appropriate reside passage.

So those are the challenges we face, like you said, it's really simple. If you can get them a compelling message at the right time when they're treating an IDH1 patient, the data itself is very compelling and can hopefully get them to use risk.

That's very helpful. And maybe on R-289, and obviously, this is looking forward into the future a little bit. So it's encouraging and nice that we're seeing rapid expansion into the dose expansion study no pun intended again looking to get the [indiscernible] and as we look towards the data later this year, presumably ASH, I'll say, what would you consider or how would you portray to -- the Street, what would be the important benchmarks or signals you would want to see to then be able to go to the FDA for a potential registrational study design.?

Lisa, go ahead. If you would comment Lisa, I can add a comment after.

Sure. Thanks for the question, Joe. I think it's an excellent question. I think that when we -- when you look at the current approved therapies, these are approved in patients that are transfusion dependent, either post CSA or ESA naive and we see that the state we RBCTI rates are only around 3% to 4%.

Now we are enrolling a population of much more heavily pretreated. We've got patients that have received prior metastatic and HMAs. And thus far, we're very pleased with the activity that we're seeing.

So I think that when we consider the difference in the patient population, I think if we can see more -- if we see consistent safety is what we've seen thus far, and additional evidence of activity, I think we're going to be really pleased with that.

In addition, you may recall that we saw data showing that our 289 also improves media in the patients in our study, which is not always a given. So we are very pleased with that as well.

So suffice it to say, I think there are several places we could slide in with this product. And there are very large segments across the board. I think it's exciting to have a novel agent that's completely different than what's out there. That's a very important feature, an oral agent, easy to take on a more chronic basis. .

And I think one of several positions within that landscape that Lisa discussed, I think, would be transformational for us. And we'll wait to see the data, the early data being, as Lisa said, very encouraging but we look to see that in much larger numbers at the end of this year so we can make that final assessment as to how to proceed.

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

This is Ian on wind line. On R-289, what do you see as an acceptable safety profile here? And how will that play into the dose selection for the Phase II .

Thanks for the question. I think that what we're seeing thus far is very encouraging compared to the currently approved agents. And by that, I mean, where with an elderly patient population, median age of 75, heavily pretreated.

We're seeing a very low incidence of cytopenias and infection. And I think also, as Raul mentioned, in combination with the fact that we have an oral agent, I think this is very, very encouraging.

So we're very pleased with that, and we hope that we continue to see that as we enroll more patients in the study.

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

It's Nalin on for Farjin. A couple of questions from us. For GAVRETO revenue, it seems like that it's plateauing in 1Q. What does mean the feedback from the sales emaprescribers? Any color on new patient starts versus switches? And what's the persistence rate so far? And then I have a follow-up for 289.

David, if you would have for answer the real revenue plan to give any color.

Look, I mean, I'm sorry. I know you're on for Farjin, but I did not get your name, sorry. .

It's Nalin.

Okay. Sorry, Nalin, we don't, on the call, generally provide details on specific new patient starts or persistency trends. But I'll just say it this way. What we got in GAVRETO was an asset that you have a very targeted market with high awareness of of using a targeted agent and particularly over the last couple of years, especially in lung cancer, there's been a large amount of data out there to clinicians. .

That really reinforce the use of a targeted agent in lung cancer and that's across EGFR or certainly in red, where it's shown in the NCCN guidelines that you should be using these.

So these patients are routinely tested much more so in the academic setting in the community. But when they do that, clinicians generally know that there are 2 available inhibitors and they choose either GAVRETO or the other available RET inhibitor.

And it's been our experience than just keeping the awareness out there for Brent and the availability of GAVRETO has helped to ensure our share in that marketplace. So I think what you're seeing is you're right. We saw growth last year, but you have to understand some of our growth was a very significant part of our growth was having a full year versus half year sales.

And what you're seeing now is a product that's producing on the order of $10 million a quarter, which I think is a great thing for us but we also want to make sure that we are not extending too much effort to try to grow incrementally on that when we have better opportunities, particularly with [indiscernible] So we're focused on the areas that we can grow in incremental revenue the most, and that's what we are doing with [indiscernible]

It's maybe a R-289 question as well. .

Yes. For 289 just quickly, are there specific well, if you can actually comment on the patient baseline profile being enrolled right now relative to do escalation cohorts.

So as I mentioned, we anticipate providing an update on the study at the end of the year. So those results will -- hopefully, we'll be able to do that, and those results will be available later.

Yes, we really can't comment so much on the study that's currently enrolling the expansion. What we can say is that the earlier study, the dose escalation phase was elderly, heavily pretreated, highly refractory type of patients.

Whether that evolves or not, now that we have some data out there showing that it may have some benefit is something we don't know yet, haven't shared.

There are no further questions at this time. I'd like to turn the floor back over to Mr. Raul Rodriguez for closing comments. .

Thank you so much for that. I appreciate all the questions. and for your continued interest in Rigel and what we're doing. Before we leave a so like to thank our employees for their dedication and commitment. 2026 is up to a solid start. We're pleased with the progress we've made across the business, and we look forward to updating you on future calls. So thank you very much. Have a good evening.

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

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 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?

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?

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?

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?

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.

Hi, everyone. My name is Denise Liu. I am an associate on the health care investment banking team here. So we're excited to be continuing the 44th Annual Healthcare Conference this afternoon, and it is my pleasure to introduce Raul Rodriguez, CEO and President of Rigel Pharmaceuticals.

Thank you, Denise, and thank you to our colleagues at JPMorgan for having invited us to present. I'm excited to be in front of you and sharing this story.

First, some important forward-looking statements. These statements are also available on our website. If you would review this, I'd appreciate it.

Let me tell you a little bit about Rigel. And I'd like to share with you our strategic plan going forward because I think it's what's driven us to get to this place where we are today, and I'd like to share that and then what our plans are going forward.

Our strategic plan has 4 strategic objectives: grow the commercial business, in-license and add products to that commercial portfolio, advance the product pipeline in the clinic and maintain financial discipline. All of these pieces work together very closely. They're codependent on each other. And you'll see in this story how we've used it in the last 5 years to get to this point and what our plans are from now into 2030.

So going a little back 5 years in history, really breathtaking a change from then to today. In 2020, we were a one product, one indication company, TAVALISSE in adult chronic ITP in the U.S. only. We had a very limited development pipeline. We were in a position where we were using cash on a regular basis as we sold products, as we developed some early programs as well. Fast forward 3 years -- 5 years later to 2025. We now have 3 commercial products, TAVALISSE, REZLIDHIA and GAVRETO, 4 different indications for these products. We have a development pipeline that looks very interesting, led by R289, Rigel's internally discovered IRAK1 and IRAK4 inhibitor that we're studying in low-risk MDS and yet having data that looks pretty promising at this point. And finally, we're profitable. We turned profitable in Q3 of '24. Since that point, we've generated $100 million in cash, a really good performance.

We've grown the top line. We've shown financial discipline. We've developed programs behind it to sell into the future. And you see we've made very good progress to this point. Now going into 2030s, which is what I'd like to talk mostly about on this presentation, our plan is to continue that growth for our current 3 products, add additional products, maybe a little larger than the ones we in-licensed, acquired in the past, all in hem/onc, move forward with R289, our IRAK1 and IRAK4 inhibitor, which we're currently working on in low-risk MDS. And in the future, we may work at it in other areas or an inflammatory product like this or inflammatory modulating product like this as important bearing on a hem/onc indication. I think it's a fantastic growth in the company, in the market cap of the company, in the financial position of the company, in the commercial portfolio and in the pipeline.

Here's a little bit of a story in terms of the sales history of the company. We are very successful in growing the sales of the company. We grew 35% from 2022 coming out of COVID to the midpoint that we're guiding now at $260 million. But what's exciting is what's coming in the future, 2030 and beyond. As R289, our IRAK1 and IRAK4 inhibitor, goes through its development and registrational program in low-risk MDS and subsequently in other indications, those are not small indications and opportunities. That's multi-hundred million and potentially billion-dollar opportunities. So again, an inflection will come with this company in the next 5 years. That's no less important than what we've already seen in the first -- last 5 years.

So let me tell you a little bit about each of these 4 strategic objectives, growing the commercial business. We've done that quite well, as you see here. And 2025 was really a stellar year for us. We grew the commercial business substantially. As you can see here, almost $90 million of growth in sales, tremendous. Every quarter was a record quarter for that quarter. And as you see here in Q4 of 2025, 41% growth over Q4 of last year. stupendous growth. And really, that growth was across all 3 of our products, TAVALISSE. TAVALISSE we launched in 2018. I'll tell you a little bit more about this product in a minute. And now we're still seeing tremendous growth with 47% growth in this product. It's great reaching $45 million in sales for this product. It's a great opportunity.

GAVRETO, we acquired this product in 2024. It was previously sold by Genentech, Roche via license from Blueprint Pharmaceuticals. At the time of acquisition, it was selling about $7 million a quarter. We acquired it, focused on it, educated doctors about it, and now sales are over $10 million. Really a great performance for this product and at Rigel for really a little bit more than a year.

And finally, REZLIDHIA. We in-licensed this product from Forma Therapeutics in 2022. It's for relapsed/refractory IDH-positive AML. And already, we acquired the product, completed the regulatory path, got it approved ahead of schedule, launched the product and already it's grown to nearly $10 million a quarter, substantial growth from a year ago, and there's more coming. I'll tell you a little bit each of these opportunities in sequence.

So TAVALISSE. TAVALISSE is indicated for the treatment of adult chronic ITP, which is an autoimmune disease where the body destroys its own platelets. So these patients have very reduced platelet counts, and they live in constant fear of bleeding or bleeding episodes, bruising, fatigue are chronic things that they endure. There are about 81,000 adult chronic ITP patients in the U.S., 37,000 or so of them are basically watchful waiting. They have some form of remission or a mild form of disease. They clearly have ITP because their platelet counts are greatly reduced from normal. Eventually, they will need therapies.

First-line therapy is typically a steroid. About 20,000 patients or so at any one time are on steroids, but eventually, they need other things. And that's where we're indicated for patients that have already gone through steroids in second line or beyond. That's about 24,000 patients. It's a good patient population that we're looking at there. Now when we launched the product, we launched it into a market that was pretty well established. The TPO agents that are commonly used here, there's 2 main ones, Nplate and Promacta, they stimulate platelet production in the bone marrow. And they were pretty successful. They were ahead of us by about a decade.

In addition, Rituxan is used pretty commonly, which reduces B cell counts and has a benefit in this area. So we were used in highly refractory patients, patients in fourth and fifth line primarily after those 2 agents. And that's where we were initially during launch. But over time, as clinicians become more familiar with the product and more used to using it and having some success with it. They now use us across the board. We've had great entry into third-line therapies and even some in second-line therapies. And so really across the board is where we're being used, which is fantastic because you see by these numbers, second and third line have many more patients than fourth or fifth line. And importantly, beyond that, the earlier you treat with this product, the better your results will be.

So if you use us in fifth line, you may get a 50% response rate. If you use us in third line, it's 86%. If you use us in second line, it's more like 94%. Those are excellent response rates. So once we are able to convince a doctor to try us in an earlier patient, they get great results. And then they tend to want to use it again.

Now the other benefit of the product is once you have a positive result in this -- with this product, you tend to keep that positive results over the long term. So the durability of it is actually quite good. Every patient that we have this quarter that are succeeding on the product is almost certainly going to be with us next quarter. So it's a good way to build a business where you're building on what's coming in from the prior quarter. So we build and grow the business that way. And we've been very successful in doing so.

One additional benefit we had this particular year is the Inflation Reduction Act, IRA. That helped close the large doughnut hole that precluded some patients from staying on the drug in Q1 of the year. So every Q1 prior to this 2025, we had some substantial number of patients drop out because of affordability of the product. We really couldn't help them, unfortunately. This year, with IRA, that has been addressed very successfully. That is it's much smaller number now, and it's smoothed out over the 12-month period, not just in January. The results of that is that many patients who would have dropped out did not drop out. And that helped us tremendously this calendar year. And it helped us in Q1, but those patients continued on therapy in Q2 and Q3 and Q4 and will continue hopefully on therapy in Q1 of this year. So we're excited about that.

That was really a great outcome simply because the patient you'd least like to lose is one that's succeeding on your product. And that allowed this to happen. Those patients continued on therapy. I think a good contribution. We benefited from it greatly with regards to TAVALISSE.

Let me go on to REZLIDHIA. REZLIDHIA is indicated for adult patients with relapsed or refractory AML with an IDH1 mutation. There are about 22,000 patients who are diagnosed every year with AML. And you may know, this is just a terrible disease, about 11,000 deaths every year from AML. It's a rapidly changing mutating indication where the illness is really unfortunate. Therapies work, but nothing works very long. IDH mutations are about 6% to 9% of all AML patients. So it's a minority of those cases, and they're well identified. Usually, by the time they get to the relapsed/refractory setting, they're genotyped, and so we know there are IDH1 patients. And this is a product that addresses that specific target.

Significant unmet need for these patients, and we were delighted to see the data from the clinical trial that underlie the approval for this product. This is a Phase II trial, elderly patients, median age 71. This is a disease of elderly. And we saw a CR/CRh rate of 35%, which is a very good number, a little bit better than what was available with other agents at the time. And importantly, the durability of that response was 25 months, substantially better than what was available previous to this agent. So providing good response rates and much longer durability was something that we thought was very attractive about this product. So we're currently providing this product. We've had good success in launching this product and then the uptake of the product. And it's in the relapsed/refractory setting, but I'll tell you about some of the other things we're hoping to do in other settings that we're studying in collaboration with some partners.

GAVRETO. GAVRETO is our most recent addition. It is indicated for non-small cell lung cancer and thyroid cancer for patients with a RET fusion-positive mutation. We like this product a great deal. One, it got us into a solid tumor market. And that's good. When we looked at our sales organization, they had substantial experience at other companies in the solid tumor space and lung cancer in particular. So we felt it was a product we could sell successfully. And obviously, the RET fusion patients are well recognized. They're difficult to treat. The results with RET fusion inhibitors such as this were very good and better than immune checkpoint and chemotherapy approaches that were used commonly. So we thought this was an exciting product to allow us to get into the market. It had already been on the market by Genentech for a number of years, but we thought we could do a bit better than that by focusing on it.

As you can imagine, a product of $28 million, it's not that exciting to Genentech, but a product of $28 million with some growth potential, pretty exciting for Rigel. So we acquired it, we launched it. And so far, we've had good success with this product. It's an oral once-a-day agent. The competitor is twice a day, good response rates, good durability of those response rates. And so just a very nice product to have in the portfolio.

Our focus internally is the U.S. market, the largest, most profitable market in the world. Outside the U.S., we've used partners to sell our products. So we partnered TAVALISSE with Grifols in Europe, where it's approved in most countries, with Kissei in Asia and Japan. It's approved in Japan. It's approved in South Korea. Other countries are coming and with Medison in Canada and Israel. Knight is our partner in Latin America, and we have an approval now in Mexico, and we're working towards approvals in other countries in Latin America.

REZLIDHIA is still in development, but it's -- we partnered it with Kissei in Japan, South Korea and Taiwan and with Dr. Reddy's in Latin America. And you see these collaborative efforts give us nice royalties, nice milestones and also nice purchases of material, which we sell on a regular basis at a profit to them. So attractive partnerships. The partnerships are doing well. The products are selling well in these various countries, and we're reporting regular collaboration revenues.

Let me go on to the second strategic objective in our plan, in-licensing and acquisition of products for our commercial business. Now what we're looking for is differentiated assets in hematology/oncology or related areas. We acquired REZLIDHIA in 2022, then subsequently acquired GAVRETO in 2024. And so we're looking for products similar to this, albeit maybe a little bit larger. We're a different company now than we were in '22. We're more profitable. We're cash generating. We have a strong cash position. And therefore, we want to have something even bigger than this. But we're looking at a wide range of things. In fact, this meeting is incredibly useful for us because we have a large number of meetings with companies at various stages of the deal process for looking at in-licensing something. We're looking for something that is late stage. By that, we mean having registrational data at hand. And the reason that's important is because we want to launch this product or products in '26, '27 or '28. '29, it begins a little bit, that's when we're beginning to shift our focus to our own launch of R289 in various indications like low-risk MDS.

So it's something we want to launch in the next 3 years or so. And so late stage is a necessity. And if you have the data, then we can look at the data to assess the likelihood of this being a successful drug on the market. That means if it's NDA filed, that's fantastic. If the NDA is under review, that's good. If the product is approved and already on the market, also something we may be interested in. So late-stage opportunities where we could be on the market as early as '26, but really no later than '28. That's the objective here. And it has to be synergistic with our current capabilities in the hem/onc space because we want to leverage that capability. That is we don't want to expand the capacity a lot more, add new sales forces, for example. We want this to be highly accretive and pretty quickly.

So it has to be in the doctor areas that we are interested and have presence already, hem/onc in both community or academic centers. So we're doing a lot of work here. And what this will allow us to do, if we have a drug that meets this criteria, just like GAVRETO and REZLIDHIA have, is that it's rapidly accretive. And therefore, our cash generation from our business is all that higher, allowing us to do even more in terms of pipeline development.

Our third objective, advance our development pipeline. Here, let me say a few words about olutasidenib, our IDH1 inhibitor. We're focusing on strategic collaborations here. We put collaborations with MD Anderson, and they're looking at studies with this product in combination or as monotherapy in AML, including frontline AML, where we do not have an indication, MDS, high-risk and low-risk MDS, CCUS, CMML and MPN as well. So these opportunities, we're studying in this area. We should be generating data, perhaps not this year, but maybe next year, we'll be able to share the profile of this product and really elucidate the benefit of olutasidenib, our IDH1 inhibitor.

Skipping one down, in MyeloMATCH, We recently announced That we're working with MyeloMATCH. they're going to be launching a frontline study in first-line AML and frontline MDS as well. And that will be a larger study funded by the NCI and NIH. That will be very beneficial because that's a market that we're very interested in. And then the Connect organization is studying this product in high-grade glioma. So a number of collaborative arrangements where we're hoping to really elucidate the product, publish information and perhaps get listings for these various areas. Our internal focus though is R289, our IRAK1 and 4 inhibitor, where we're evaluating the product in a Phase Ib study in lower-risk MDS. We've been granted Fast Track and orphan designation by the FDA, which is very helpful as we work on this product and try to move it forward. And as the year progresses, we'll share with you some of the other indications that we're interested in, tell you a little bit more about that.

So IRAK1/4 in lower-risk MDS. So what's very interesting, and you may know this, as the last 10 years have progressed, the appreciation for the role of inflammatory process in driving cancers and hem/onc conditions has been more and more established. So that, for example, in low-risk MDS, it's understood that a very pro-inflammatory environment in the bone marrow is central to the growth of MDS. And therefore, the idea is, well, why don't we address that component? If we had an agent that was very effective in modulating the immune component in the bone marrow, that would be a really interesting approach and a very novel approach to treating potentially low-risk MDS. IRAK1 and IRAK4 allows us to do exactly that. IRAK1 and IRAK4 inhibitors inhibit the signaling of the toll-like receptor TLR as well as IL-1 family of signaling, reducing that inflammatory cytokines. And that's exactly what you would want to do in a disease such as low-risk MDS, potentially other diseases in hem/onc, where there's an important pro-inflammatory component to the disease.

So this agent allows us to do something really, really novel that is suppress the inflammation in the bone marrow and restore normal hematopoiesis. These patients with low-risk MDS have an overburdened bone marrow by this inflammation and are unable to produce a normal count of red blood cells. By using this agent, we may be able to resolve that problem. It's the word. 289 is a prodrug of 835. In the gut, it converts fully to 835 and in circulation, 835 is the agent that does all the work. What we've shown with 835 is that it's able to block inflammatory cytokines in normal healthy volunteers quite successfully.

Looking at -- we take normal patients, give them an LPS protein, cytokine storm occurs. What we've shown is that we're able to dramatically reduce that cytokine storm with 835. We've also shown that IRAK1/4 is much better than just IRAK4 in doing this. With IRAK1/4, you're able to completely inhibit major pro-inflammatory players like TNF, IL-6. IRAK4 only allows you to do that partially. So we think, especially for hem/onc indications, this is a fantastic tool to try this in low-risk MDS, are we able to achieve normal hematopoiesis with this product. And so we've launched a number of different trials, a trial that we're going to tell you a little bit about. But first, let me tell you a little bit about the landscape of low-risk MDS.

As I said, MDS is a disorder of hematopoiesis, where the inflammation crowds out normal hematopoiesis. These patients are anemic, have other cytopenias and have a variety of other problems that ensue. Our goal is to limit transfusion dependency that is take transfusion-dependent patients and get them to transfusion independence or greatly reduce their transfusion burden. And to date, there are agents available for this indication, but there's substantial room for improvement. First line is typically erythroid-stimulating agent like an ESA. And failing that, they go on to an agent like luspatercept, which is a very successful product. This product sells $2 billion annually. Really a great product in terms of that sales level. However, it only produces about a 40% response rate. That is 60% of patients on luspatercept do not respond.

So that's a real opportunity. Failing luspatercept, they typically go on to an HMA. The response here are even worse, 18% to 20% responses for HMAs. So again, agents are available, but boy, they leave a lot to be desired in terms of their efficacy. In some cases, even their AE profile is a little bit toxic. So we view the entire spectrum here from post-ESA pre-luspatercept as an opportunity after luspatercept, 60% patients don't succeed on that product or even afterwards, but that's a much smaller market. We're interested in the middle here, and we're interested in the left side of this slide because those are $1 billion-plus opportunities.

One thing to say about this slide, there are about 12,000 patients, maybe a bit more than that with this indication. So a good number of patients available to treat here. So that's why these drugs are potentially billion dollar drugs. There are sizable opportunities in terms of this. I've already told you the mechanism of action is a good fit to the understanding of this disease. And I'll tell you a little bit about our Phase Ib study, which is what currently is underway. So this is an open-label, multicenter study being conducted in the U.S. And it has a dose escalation phase. I've shared the data with you from the dose escalation phase in a minute, but you dose up from a low dose to a more higher dose. We completed this phase of the study last year, we shared the results at ASH.

Last year, we also selected 2 doses, 500 QD and 500 BID for a dose expansion. Here, we're going to add up to 20 patients in each of those 2 arms, and we'll see which of the 2 are the best in terms of moving forward. We'll pick one of those 2 doses this year in the second half of this year, and then we'll initiate a registrational study in 2027. Now the registrational study is still in discussion with FDA in terms of what that would look like. But almost certainly, we'll be taking patients that are transfusion dependent and getting them to transfusion independence as the primary objective, not too different than the Geron imetelstat product showed in recent study. So very similar to that. So it's a pretty straightforward thing that we have to do here.

One other thing before I leave this slide, I want to point out to you, once we know the dose that we're going forward with, we're going to start a small study in the post ESA pre-luspatercept area and show how we do in that field because that's very interesting. Obviously, it increases the size of the opportunity if we show success there. So maybe about 12 months from now, we'll have the expansion phase data in hand, maybe a little less than that. And soon after that, we'll have this other additional post-ESA study. I think that really flushes out well what the opportunity is in the order of magnitude of what 289 could do in low-risk MDS, and we'll have a registrational plan in hand that we're going to start working on and getting it approved into the future. So that's an exciting time for this product. I think we have exciting data coming in later this year, exciting additional things to tell you about in terms of other areas we'd like to share with you.

So here's the data that we shared at ASH. The patients that we studied were at the extreme right of that landscape. They were heavily pretreated elderly patients generally with high transfusion burden. The median age was 75 years old. They had failed previously 3 other therapies. 3 had an HMA, 76% luspatercept. ESA is about 73%. So pretty treatment refractory patients. As the clinician, Dr. Garcia-Manero of MD Anderson, stated at the podium at ASH, it's remarkable, and he used that word remarkable a number of times that you see any responses with these patients. I'll show you what we got in a minute.

The safety profile looked good, well tolerated, low incidence of grade 3 or 4 cytopenias, low incidence of infections. I'd like to highlight in peach there, the 500-milligram QD in the middle and in the right side, the 500-milligram BID, where you see very small numbers of Grade 3/4 AEs in both of those cases. In fact, the things you see most frequently is anemia. Remind you, this is a disease of anemia, so you should see anemias because it's just a part of the disease. But a very acceptable safety profile thus far. I think well-tolerated drug. So we're pleased with those 2 doses, and that's one of the reasons we selected them to move forward into further study.

We have here some PK analysis of R289 or 835 as it circulates. What we've shown is that at 500 milligrams or above, QD or above is where we have exposures that we think are good to see a response. And in fact, that's where we've seen responses. We've seen responses at 500 and above, and I'll show you some of those responses. But it's good to see this is where it is. The lower doses in that, probably not adequate. Exposures were low, and we didn't see any responders, not surprisingly. So it's good to have that correlated. Apologies for the complexity of this slide, but I think it's really telling.

This is a chronological view of how we dose these groups starting at low doses and then going higher. What is important here is in the second bullet point. We had 18 patients that were transfusion-dependent and evaluable and the doses above 500, the dose that I said were about where you should see results. And within those patients, we had 6 or 33% responses in getting patients to transfusion independent. That's a pretty good result, especially considering the highly refractory nature of these patients. If you look at the 500-milligram BID dose group, we had 5 patients that were transfusion-dependent and evaluable. We had 2 responders there. So that's 40%. So that's the order of magnitude that we're talking about thus far.

Now I can see this is a small data set as yet, and we're working to expand this data set substantially in the dose expansion cohorts, where we'll add at least 20 in each of those 2 dose groups, and we'll have that data later this year. So exciting to be able to show some benefit in these patients. The clinicians are excited. People that are involved with the trial see this as well. This is obviously showing some benefit, and it looks tolerable in terms of the safety profile. So it's a great place to be. A little bit more detail maybe in the hemoglobin levels. What you see here is that we're able to raise hemoglobin quite nicely, 2.9 to 6.1 in patients that had a response. And you want this to correlate with that, and it does. So it's useful showing that the patients have a reduction in transfusions or no transfusions for a while. And their hemoglobin goes up as they're being treated with the product. So it's very exciting to have this as a corollary. No doubt this will be probably a secondary endpoint in some future study.

So in summary, well-tolerated drug studied in very elderly, very heavily pretreated patient population. And we had responses of about maybe 33% in patients who had adequate doses above 500 milligrams QD and who had -- were transfusion dependent. So it's a good place to be in terms of the product and future study. And it's exciting that it's in a category where there's substantial need as yet and where there's substantial opportunity commercially.

Next steps for this drug in this area is to complete enrollment of the dose expansion and select which of the 2 doses to go forward into a registrational study, share the top line data with you sometime at the end of this year. And we also are going to start that post-ESA pre-luspatercept study to generate data in that very early setting because that will be an exciting data set to have. And we'll discuss with FDA what the registrational plan is and launch that study in 2027.

Now this is a good place to start, but it's not the only place we want to go with this molecule. We think that the inflammatory cascade, a pro-inflammatory condition is important in a number of other hem/onc indications. And we're looking at quite a number of those in terms of where else do we want to go, where can we redeploy this agent. And as the year progresses, we'll come back and tell you a bit more about those opportunities, but we'd like to launch studies in those in sequence. Maintain financial discipline. Well, we've done that quite well. We've grown the top line, as you see here on this chart, almost very substantially on a quarterly basis, all products growing, TAVALISSE, REZLIDHIA and GAVRETO. And as the product sales have grown, what you see is pretty small growth in terms of the expense line. 40 -- low 40s is the number for the last 1.5 years or so, which is really very good. Top line keeps growing positively and strongly, discipline on the OpEx line. The result is we turned profitable, and we are starting to generate cash. You see we've doubled the cash position of the company to $154 million in calendar year '25.

So we're in a strong financial position as a result of this, and we have a place to spend this cash, and I think we will. And I think it will lead to transformative products that are coming to the market sometime at the end of this decade. So our key priorities for this year is grow the commercial business, continue that growth, in-license another molecule to add to that to yield further cash flow in the future, near future, beginning perhaps as early as '26, advance the pipeline focused on 289 and in low-risk MDS, have that data, initiate the post-ESA study, discuss with FDA what's going to take to get this product approved and prepare to launch that registrational study, discuss with you other indications that we'd like to pursue with this. And finally, maintain financial discipline.

We've given guidance. Our guidance is here, $275 million to $290 million in total revenue, comprised of $255 million to $265 million of product revenue and about $20 million to $25 million in contract revenue. And importantly, continue to be net income positive for the year. And that's important also because we still think we can have the ability to do that and still fund the clinical studies that we discussed today and other new studies in addition to that. Again, the company is in a very strong financial position, a very strong position in terms of the commercial business, strong position in terms of our ability to introduce new products from external sources and ability to generate a pipeline that I think will transform the company in the not that distant future. So thank you. I'd like -- I think we have about 5, 6 minutes.

If anyone does have a question, we have a mic to pass around. So just raise your hand. I can kick it off with the first question.

Sure.

It's great to see that R289 is progressing well. And you alluded to some updates in the near future about future indications and expansion. Is there any other detail that you can give us about expanding this product or mechanism beyond lower-risk MDS?

Yes. Well, I can't tell you the exact indications yet because that's coming. We're still working on that. I'll tell you some of the things we're interested in. We think that the inflammatory modulation that this product offers is unique. Interestingly, we are the only company in the clinic with a true IRAK1/4 inhibitor. That is we have a substantial lead in this area over anybody else. And other companies have studied IRAK4 inhibitors, primarily in inflammatory conditions, but not in hem/oncs yet. And I think that's a tremendous advantage that we have. And we have a tool, a molecule in 289 that I think is showing good safety, good exposures and initial positive results in terms of efficacy in one indication. So it behooves us to step on the gas in that and go into other indications as well. So what we're looking for is places where this mechanism is a good fit to that indication. There's quite a number of this.

In addition, it has to be sizable. We're not interested in a $10 million or $50 million opportunity. We're interested in a multi-hundred million, billion dollar types of opportunity, and I think they exist. And we're interested in something where there is a medical need. There are some indications where this may fit, but it's such a well-served market that it may not be the right place to go with it. So there has to be a medical need for it. It has to be a good fit to mechanism in that indication. And there has to be something that is sizable enough to matter to us. So those are some of the criteria we're looking for, obviously, other areas, other things as well. But I think we put a lot of effort into thinking about this, and we'll be able to share some later this year in terms of what that might be. And soon after, hopefully, begin to launch Phase II studies in those new indications.

Are there any questions? Just to follow up on that. So you mentioned the significant unmet need in -- sorry, in lower-risk MDS and just how it's very targeted. It's the only one in clinic right now. How should we think about how it compares to other available therapies? And what should we focus on for the remainder of the year?

Yes. So in the landscape of low-risk MDS, as I mentioned, the approved agents are luspatercept and then imetelstat, the Geron product that was a recent approval and the HMAs. The response rates for luspatercept is about 40%. It's a successful drug. Like I said, $2 billion in sales is fantastic. But 40% is still not 100%, it's not higher. We have a very different mechanism than luspatercept. And that gives us some opportunity that in -- if we're able to show equivalence to luspatercept, we are competitive in that field pre-luspatercept. And that's what we'd like to show with that study that we're going to study.

But in the post-luspatercept market, because we have a different mechanism than them, that's a very attractive market also because a large number of patients don't succeed on luspatercept and they need something else. That's something else that they currently use is HMAs, which I said 18%, 20% response rate. That's pretty low a response rate. I think we can beat that. Already in even more refractory patients, we're showing about a 33% response rate. So already, we're showing benefits that's well above what an HMA can give you.

So we're really optimistic about our ability to show benefit and compete successfully along that spectrum, especially in the middle post-luspatercept, but potentially even in the pre-luspatercept market. And like I said, no one else has a mechanism such as this. And we believe and it's well established that the pro-inflammatory environment in the bone marrow is a central feature of routing out normal hematopoiesis. And if we can restore that, these patients will be able to produce normal red blood cell counts.

Just pivoting a little bit to the commercial products. I just was wondering if you could tell us a little bit about the drivers and your confidence in growing the 3 commercial products.

Yes. So we've had tremendous success in growing the commercial business. TAVALISSE, we launched it in 2018. So already, it's 7, 8 years into the market. But keep in mind, a couple of those years were COVID years where things were flat, we were not on in the field. The business in ITP, the other products also were flat. But coming out of COVID, we were able to really reestablish that growth. And it's because doctors are now more familiar with the product, we're using it more broadly. And that helped tremendously drive the growth of the product. And as I said, earlier line usage is important because earlier line usage means more success for that clinician. More success with that clinician means they're likely to use it in another person -- another patient in the future.

Now one thing about this indication, it's a rare disease indication. So a typical doctor may have maybe 4 patients with ITP. It's not like breast cancer or lung cancer or prostate where there's lots and lots of patients. It's simply not like that. There's a very limited number of patients. So clinicians have just a few patients they're treating. So it's not even -- for any one doctor, probably once or twice a year is when they need a new agent. So you really have to be on top of this area to be able to intercede when that decision comes. And so that's taken years of establishing the product, lots of discussions, lots of clinician marketing. And -- but I think it's been a successful effort because now clinicians are comfortable with it. They talk about it as part of the usual paradigm for treating ITP, and that's taken years to get here. But we're benefiting from it now.

Like I said, this past year, the IRA really helped us in terms of retaining patients that formerly would have dropped out. And that's been a good help for us, and we expect that to continue forward. So ITP is an important indication, and this product is central to our -- it's a cornerstone product to our success going forward.

Thank you. And I think we are out of time. So with that, I just want to thank the entire Rigel team for the work you do and a great presentation. Thank you, Raul.

Thank you so much, Denise.

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 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 2024, the first full quarter GAVRETO was commercially available from Rigel. The year-over-year growth was driven by an increase in new patients and carryover demand. GAVRETO is now a stable business that is consistently generating more than $11 million per quarter.

And lastly, for REZLIDHIA, we reported $8.3 million in net product sales, an increase of 50% compared to the prior year period, reflecting record demand. During the quarter, we saw an increase in both breadth and depth of prescribers. We continue to believe there is a significant opportunity for growth because our data in the post-venetoclax patient population is a clear differentiator.

Moving to Slide 10. We continue to work on expanding access to our products in markets outside the U.S. TAVALISSE is commercially available in Japan, in Europe under the brand name TAVLESSE, and in Canada and Israel via partners, Kissei, Grifols and Medison. In addition, Kissei’s licensing partner, JW Pharmaceutical Corporation, launched TAVALISSE in South Korea in early July as our partners continue to pursue regulatory approvals for TAVALISSE in new markets.

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. We are pleased that access to our products is expanding outside the U.S., and we continue to explore other opportunities for partnerships to bring our products to other markets around the globe.

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

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 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 earned royalties. This brings our total revenue for the third quarter to $69.5 million.

Moving to the next Slide 26. Our cost of product sales was approximately $4.8 million for the third quarter of 2025. Total cost and expenses were $41 million compared to $41.3 million for the same period of 2024. The decrease in costs and expenses was mainly due to lower cost of product sales as the prior period included a sublicensing fee, partially offset by increased research and development costs driven by the timing of clinical activities related to olutasidenib and R289 and higher personnel-related costs.

We reported net income of $27.9 million for the third quarter compared to $12.4 million for the same period of 2024. We ended the third quarter with cash, cash equivalents and short-term investments of $137.1 million compared to $77.3 million as of the end of 2024.

Now for our financial outlook for 2025. Based on our strong performance to date, we're raising our total revenue guidance to approximately $285 million to $290 million, an increase from the prior range of $270 million to $280 million. This includes updated net product sales expectations of approximately $225 million to $230 million, an increase from the prior range of $210 million to $220 million, and contract revenues from collaborations of approximately $60 million. We continue to anticipate reporting positive net income for the full year 2025 while funding existing and new clinical development opportunities.

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

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.