RIGL - NASDAQ

Greetings, and welcome to Rigel Pharmaceuticals Financial Conference Call for the First 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. Fury. You may begin.

Welcome to our first quarter 2025 financial results and business update conference call. The financial press release for the first quarter 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 quarter one 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 would like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez. Raul?

Thank you, Ray, and thank you, everyone, for joining today. Also with us today are Dave Santos, our Chief Commercial Officer; Lisa Rojkjaer, our Chief Medical Officer; and Dean Schorno, our Chief Financial Officer. Now beginning on Slide 4, we will provide an overview of Rigel's business and our results for the first quarter of 2025. I want to start the call today by highlighting our strong start to the year. Today, for the first quarter of 2025, we reported year-over-year net product sales growth of 68% from our expanding commercial portfolio. In addition, we increased collaboration revenue from our ex-U.S. marketing partners. With total revenue of $53.3 million for the quarter and continued financial discipline, we were able to generate $11.4 million in net income this quarter. Now this is a time when the general business environment is challenging, especially for the biotech market, but highlights the robustness of our corporate strategy and consequently, our unique position. Rigel is a growing, profitable company with important clinical opportunities at hand that we are able to fund ourselves. On this call, the team will provide you with greater details on our position and this quarter's results. Dave will provide an overview, update on the strength of our growing commercial business that now includes 3 commercial products after the acquisition of our latest product, GAVRETO. Lisa will provide updates on the advancement of our development pipeline, including R289, our novel and selective dual IRAK1 and 4 inhibitor. R289 is currently being evaluated in a Phase Ib clinical study in patients with relapsed or refractory lower-risk MDS. She will also highlight our plans to expand olutasidenib in the planned -- with the planned initiation of a Phase II study in recurrent glioma. Beyond these Rigel-led development programs, we also remain committed to evaluating new opportunities to expand our hematology and oncology portfolio through business development as we did with RE

Thank you, Raul. On Slide 6, you'll see our 3 commercial products, TAVALISSE, GAVRETO and RE

Thanks, Dave. I will now provide an overview of our pipeline progress and plans for the remainder of the year. I'm on Slide 12. From our development pipeline, we're particularly excited by the progress in the clinical development of R289, our novel dual IRAK1 and IRAK4 inhibitor in lower-risk myelodysplastic syndrome, or MDS, and olutasidenib in mutant IDH1 recurrent glioma. Beginning with R289, our Phase Ib study in patients with relapsed/refractory lower-risk MDS is progressing well, and we're currently enrolling dose level 6. We look forward to providing updated data from this study in the second half of this year. From a regulatory perspective, the granting of both Fast Track designation for the treatment of patients with previously treated transfusion-dependent lower-risk MDS and Orphan Drug designation for MDS is an acknowledgment by the FDA of both the unmet medical need of the lower-risk MDS patient population and the potential of R289. Furthermore, as part of Rigel-sponsored development programs and alongside our partners, MD Anderson and the Connect Cancer Consortium, olutasidenib is being evaluated in new indications. We believe olutasidenib has potential in several cancers where mutated IDH1 plays a role, such as glioma, additional AML segments and MDS, either as monotherapy or in combination. We expect to initiate a Rigel-sponsored Phase II study to evaluate olutasidenib in recurrent glioma later this year. In addition, all 4 clinical trials under our MD Anderson collaboration are now open for enrollment as is the CONNECT TarGeT-D study, evaluating the combination of olutasidenib with temozolomide as maintenance therapy in adolescents and young adults with IDH1 mutated high-grade glioma. Consistent with our strategy and evidenced by our acquisitions of olutasidenib and pralsetinib, we remain focused on evaluating potential opportunities to expand our portfolio by in-licensing or acquiring products that would be a strategic fit for our hematology and oncology focus. Now I'll spend a few moments on our R289 program. I'm now on Slide 14, which presents an overview of the value proposition of R289 in lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the U.S. With recent development efforts in lower-risk MDS focusing primarily on first-line therapies, there's a high unmet need for next-line therapies, particularly for previously treated 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 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 being currently evaluated in the clinic, is the oral prodrug that is rapidly converted to R835 in the gut. As I mentioned, R289 has both FDA Fast Track and Orphan Drug designations, 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 and their willingness to collaborate with Rigel in the development of R289. In addition, R289 has thus far demonstrated a promising preliminary clinical profile in a Phase Ib study. The initial dose escalation data that were recently presented at the ASH Annual Meeting demonstrated promising preliminary safety and clinical activity in elderly, heavily pretreated patients with relapsed or refractory lower-risk MDS. On Slide 15, we outline 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. Aside from transfusions, initial therapies include erythropoiesis stimulating agents, or ESAs, if patients are eligible and luspatercept. Imetelstat was also approved last year for ESA failure, high transfusion burden, lower-risk MDS. With 8-week transfusion independence rates approaching 40% with luspatercept and imetelstat, many patients require an alternative treatment option. Although hypomethylating agents or HMAs are approved, the percentage of patients achieving transfusion independence is low. Therefore, there is a high unmet need for safe, effective treatment options following failure of approved therapies, particularly for previously treated transfusion-dependent patients. On Slide 16, you'll see the design of our ongoing open-label dose escalation, dose expansion Phase Ib study in relapsed/refractory lower-risk MDS patients with either symptomatic anemia or transfusion dependence. Primary endpoints are safety and selection of the recommended Phase II dose and secondary endpoints include transfusion independence, hematologic improvement, response rates and PK. Enrollment is ongoing into dose level 6 in the dose escalation part of the study, evaluating a dose of 500 milligrams twice daily. Once enrollment of this cohort is complete, the plan is to select 2 doses to be compared head-to-head in the dose expansion part of the study to optimize selection of the recommended Phase II dose for further evaluation. In addition, once the recommended Phase II dose has been determined, an exploratory cohort of first-line lower-risk MDS patients will be opened to evaluate R289 at that dose in an earlier line of therapy. Initial data from the study was presented at ASH in late 2024. On Slide 17, you'll see the initial safety data that was presented. To put the safety data into context, this was an elderly, heavily pretreated patient population with a median age of 76, more than 70% of whom had received either luspatercept or an HMA. Almost three quarters had a high transfusion burden, meaning they frequently received red cell transfusions before they enrolled in the study. In this population, R289 was generally well tolerated with low-grade nausea, diarrhea, fatigue, chills and pruritus being most frequently reported overall. Nausea and diarrhea were also 2 of the most frequently reported related adverse events that are indicated in the table on the slide. Overall, the most frequently reported grade 3 or 4 adverse events were anemia, decreased platelet count, pneumonia and increased ALT, occurring in only 2 patients each. So thus far, what we're not seeing is a high incidence of cytopenias and infections, which is encouraging. On Slide 18, we show the preliminary efficacy data. The swimmer plot shows each patient and the red cell transfusions by dose group, starting with the lowest dose group, 250 milligrams daily on top. Per the IWG 2018 criteria, the transfusion history for each patient was collected for 16 weeks prior to R289 administration to establish the baseline transfusion frequency for each patient shown to the left of day zero, which is indicated by the red arrow. 18 patients were evaluable for efficacy, meaning that they had received one or more R289 doses and had at least one efficacy assessment. Red blood cell transfusion independence lasting 8 weeks or longer was achieved by 3 patients, one receiving 500 milligrams daily and 2 receiving 750 milligrams daily. Red blood cell transfusion independence lasted for more than 6 months in 2 patients and 1 patient also achieved a marrow complete response. The median duration of transfusion independence was 29 weeks. In addition, one high transfusion burden patient receiving 500 milligrams daily achieved a minor HIE response with a 64% reduction in red cell transfusions compared to baseline. Looking at PK, we noticed that at R289 doses of 500 milligrams once daily and higher, R835 plasma concentrations reached or exceeded those correlating with 50% or 90% LPS-induced cytokine inhibition that was previously observed in healthy volunteers. And what's interesting is that at these doses, i.e., 500 and 750 milligrams once daily, 40% or 4 out of 10 evaluable transfusion-dependent patients achieved transfusion independence. Moving to Slide 19, you see the summary of the responding patients. A few things to highlight here. The majority of responding patients were high transfusion burden at baseline and had received a variety of prior therapies, including luspatercept, hypomethylating agents and even some experimental therapies. Both patients achieving durable transfusion independence lasting more than 6 months, patients 4 and 10 were high transfusion burden at baseline and had received HMAs. Beneath the table, we see the hemoglobin levels over time for the 3 patients that became transfusion-free. Although patient 10 in the middle eventually lost their response following a drug interruption and dose reduction, on the background of transfusion independence, peak hemoglobin increases ranging from 2.3 to 5.6 grams per deciliter compared to baseline were observed, indicating that R289 has the potential to correct anemia, providing support for its evaluation earlier in treatment. In summary, the initial data is encouraging, showing R289 is generally well tolerated with promising signs of preliminary activity in heavily pretreated transfusion-dependent patients. We look forward to sharing additional data from the study in the second half of this year. Now I'll shift focus to olutasidenib, our IDH1 inhibitor. Beginning on Slide 21, glioma is an area that is incredibly challenging, where there's not been much advancement in therapeutic options. Diffuse gliomas are the most common primary brain tumor in adults, affecting approximately 20,000 in the U.S. each year. IDH1 mutations occur in about 70% of patients with grade 2 and 3 glioma and are found at up to almost 35% of adolescent and young adult patients. Unfortunately, most of disease recurs and there is no standard of care therapy for relapsed patients. The recent approval of vorasidenib, an IDH1 and 2 inhibitor in Grade 2 low-grade gliomas has highlighted the potential for IDH inhibitors in glioma. Olutasidenib was previously evaluated in the Phase Ib/II study in 26 patients, which was previously published in the Journal of Neuro-Oncology. Two patients with high-grade glioma achieved partial responses and both with enhancing tumors and 10 patients achieved stable disease for a disease control rate of 48%. This clinical proof of concept supports further evaluation of olutasidenib in glioma. Moving to Slide 22, we outline our development approach in glioma. Last year, we entered a collaboration with the Global Neuro-Oncology Consortium CONNECT. 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 IDH1 mutation positive high-grade glioma. This study is open for enrollment. In addition, we're on track to initiate a Phase II clinical study in recurrent glioma later this year. We think this is an important opportunity as there is a significant unmet need in this patient population. We, along with CONNECT, are excited about olutasidenib's potential to provide a much needed new treatment option to this underserved patient population, and we look forward to the data generation from the CONNECT study in addition to our planned study in recurrent glioma. On Slide 23, you'll see another important collaboration, our strategic alliance with the MD Anderson Cancer Center to advance olutasidenib more broadly into AML, MDS and beyond. All 4 studies included in this collaboration are open for enrollment, and we look forward to sharing updates from this collaboration in the future. Turning to our partnered program. On Slide 25, as Raul mentioned, we're very excited about the Lilly collaboration for ocadusertib and the CNS penetrant program. The RIPK1 inhibitor programs are progressing well with our partner, Lilly, and we're very pleased with the program's potential. RIPK1 is implicated in a broad range of inflammatory cellular processes and plays a key role in TNF signaling. 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. Phase IIa enrollment is advancing well. The preclinical CNS penetrant RIPK1 inhibitor program is also progressing toward lead candidate nominations. Moving to Slide 26. We outlined several upcoming milestones for our development programs in 2025. For our ongoing R289 program in lower-risk MDS, we expect to complete the dose escalation part of the Phase Ib study. We then plan to initiate the dose expansion phase later this year. Also during the year, we plan to seek health authority input on the registrational path for R289, and we're anticipating presenting updated dose escalation data in the second half of the year. Then for olutasidenib, we plan to initiate a Phase II clinical study in recurrent glioma by year-end. We'll provide you with more details about that study later this year. In addition, we'll continue to support the 4 MD Anderson studies and the CONNECT study. We're excited about the potential of our development programs and look forward to providing updates in the future. Now I'll pass the call to Dean to discuss our financial results for the quarter. Dean?

Thank you, Lisa. I'm on Slide number 28. We reported net product sales of $43.6 million for the first quarter, growth of 68% year-over-year, including TAVALISSE net product sales of $28.5 million, a growth of 35% year-over-year, GAVRETO net product sales of $9 million. As a reminder, GAVRETO became available from Rigel in June of 2024, and we reported RE

Thank you, Dean. Moving on to Slide 30. We made significant strides over the past 3 years to expand our commercial portfolio via in-licensing or acquiring assets that fit our commercial capabilities and portfolio focus. We have a proven track record of delivering top line growth as evidenced by the 32% compound annual growth rate or CAGR in revenue growth from 2021 to 2024. This revenue growth enables us to fund our business and our strategic priorities, including to continue expanding our hematology and oncology business. And we're confident in our expectation of approximately $185 million to $192 million in net product sales this year. Turning to Slide 31. For the remainder of 2025, our priorities are clear, grow our commercial business, advance our development pipeline, identify new pipeline opportunities and continue to maintain financial discipline. We anticipate growing our net product sales in 2025 by approximately 30% year-over-year. We remain focused on advancing our Phase Ib clinical study evaluating R289 for the treatment of patients with lower-risk MDS. And we are on track to publish updated data at a medical meeting late this year and initiate the dose expansion phase of this study by year-end. For olutasidenib, we plan to initiate a new Rigel-sponsored Phase II study in recurrent glioma while continuing to support our strategic collaborations with both MD Anderson and the CONNECT organization. With our anticipated strong revenue growth, financial discipline in 2025, we will continue to invest in our development programs, but also expect to report positive net income for the full year. Finally, on Slide 32, our successful execution of our corporate strategy has resulted in Rigel being uniquely positioned in building a leading hematology and oncology business in a profitable and sustainable manner. And with that, I'd like to thank you for your interest, and we will now open the call to your questions. Operator?

Thank you. [Operator Instructions] And our first question comes from Kalpit Patel with B. Riley Securities. Please state your question.

Hey, good afternoon and thanks for taking the question. I had one on the TarGeT-D program that you have ongoing in high-grade glioma. I guess you have two different plans here for glioma. You have that study running and then you also have the planned company-sponsored Phase II trial in recurrent glioma. Can you help us clarify the objectives and perhaps the design differences between the two? And longer term, what signal do you want to see in the TarGeT-D program to justify moving forward in one program or the other?

I'll ask Lisa to take a shot at it. And also, I think just to start that there's two different studies here, two different patient populations. The TarGeT-D program, which we're delighted. It's an umbrella study that was already underway, which allows us to add our product to that one. So logistically facilitates the start and initiation of that study. It's a bit different population than what we're contemplating in our own clinical study. Maybe you can just give ore color, Lisa.

Yeah, sure. Thanks for the question, Kalpit. So yes, as Raul mentioned, we're supporting this - the CONNECT umbrella study. Our arm is looking at the combination of, as I mentioned, olutasidenib with temozolomide as maintenance. So in the maintenance setting. So these will be targeting patients that are post surgery and radiotherapy. So it's temozolomide, olutasidenib for 1 year, followed by 1 more year of olutasidenib monotherapy maintenance. And this is going to be focused on patients with Grade 3 astrocytoma, so looking for an impact on progression-free survival. We're happy to be working with CONNECT on this one. It's a unique population. These are adolescents and young adults. We're looking to kind of help expand that site - the sites also because they're a pediatric organization potentially into more adult sites. And we think it complements our strategy nicely with our plans to go into recurrent glioma. Now we're not discussing any of the details about our plans yet, but we will be sharing more about that later on in the year.

Okay. Wonderful. And then one quick question on the patent litigation that you resolved with Annora for TAVALISSE. I guess, are there any other ANDA filers that investors need to be aware of?

No. There's no ANDA filers that we are aware of.

Okay. Got it. Thank you very much for answering questions.

Thank you, Kalpit.

And your next question comes from Joe Pantginis with H.C. Wainwright. Please state your question.

Hi. Good afternoon. Thanks for taking the question. So first, when you're looking at your product sales, and it's nice to see your core revenue from TAVALISSE continuing to expand. GAVRETO increased, you saw some - a little bit of increase or from RE

Yes. Why don't - Dave, maybe you can comment, and I know Dean has a comment on that as well.

Sure. Thanks for the question, Joe. Actually, for Q1, we are quite pleased with our progress on all 3 brands. We grew demand for all 3 brands. And so I think we're right where we want to be, which is why we're sticking with our guidance. And I think our signs for Q1, obviously, we did go into it kind of prepared for the changes, particularly with respect to the Inflation Reduction Act. And I think we did a really - the team did a terrific job making sure that patients understood the changes and all of the factors that would enable them to have medications in - at the beginning of the year. And I think we pulled that through quite successfully and our demand continued to grow.

Yes. I think Dave has that right. So we're pleased with the demand side of the equation, and we did see the expected drawdown in inventory, resulting in still a 68% year-over-year growth. So a strong quarter for us.

All right. Thanks for the info.

Thank you, Joe.

[Operator Instructions] And your next question comes from Farzin Haque with Jefferies. Please state your question.

Hi. Thank you for taking my question. I had a couple. I guess I'll start with R289. Are you saying more on how you're setting expectations for the split doses that you're exploring post ASH, like with the dose level 5 and 6? And then just to clarify, for advancing to the recommended Phase II dose, would you need regulatory feedback on dose escalation data set?

Yes, I'll let ask Lisa to comment on that.

Yes. Thank you for the question. So in terms of -- we don't really have any expectations. I'm not sure I understand question. We have switched -- I'll provide an answer, and you can tell me if I've answered it satisfactorily. We switched some time ago from once daily to twice daily dosing because we thought that biologically, it makes more sense to maintain a tonic suppression of inflammation as opposed to having this once daily like peak and trough and peak and trough in terms of - from that aspect. And that's why we switched to explore the BID dosing. We're progressing up. We had some preliminary data on the 250 BID. We've now completed enrollment of the 500, 250 and now into the 500 BID. So as I mentioned, we're going to be updating data at ASH, share that with you later on this year. I think we'll share some PK data as well that I think will contribute to what I mentioned in terms of it may be better to kind of have that more prolonged exposure as opposed to the up and down. With respect to the - you mentioned the alignment or how to select the doses. So as you're aware, the FDA has encouraged companies now to align with Project Optimus to ensure more robust dose selection early before advancing into Phase II. So consistent with that, we will be seeking input from the FDA, aligning with them on the 2 doses for comparison in the dose escalation part of the study, and we'll be doing that midyear.

Got it. That makes sense. And then for a follow-up on the earlier question on the ANDA filing. So Annora is one example, and they cannot enter the market, I think it mentioned prior to 2Q '32. But if there are additional ANDA filers in the future, could they have an earlier market entry? Or is that 2Q '32 pretty much when you should see a new entry?

Yes, you can get second ANDA filers, and they would need to defeat the patents, which in order to enter the market earlier than the current last list of patent, which would be July 27, 2032. But there's a possibility of an ANDA filer. But once there's one entrant already where there's a settlement, it's a disincentive to second filers and tertiary filers. But it is technically possible that there could be a second fire. We haven't seen yet. No, we have not -- there's no -- we have no notice of a second filers.

Okay. Thank you.

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. Thank you.

Thank you. I'd like to thank everyone for joining us on the call today. It was the start of a very strong year. First quarter was an excellent quarter for us. We're very happy with what we were able to accomplish in this quarter. It sets us up very well for a very strong calendar year. And so for that, I'd like to thank you for your continued interest in Rigel. I'd like to also thank our employees and for their commitment to Rigel and our values, particularly our commitment to improving the lives of patients. We will keep you updated on future calls as the year progresses. And with that, have a good day.