Q4 2024 Rigel Pharmaceuticals Inc Earnings Call & Business Update

Unknown Executive: Greetings and welcome to Rigel Pharmaceuticals financial conference call for the fourth quarter and full year 2024. At this time, all participants are in a listen-only mode.

Greetings and welcome to Rigel Pharmaceuticals Financial conference call for the fourth quarter and full year 2024.

At this time all participants are in a listen only mode. A brief question and answer session will follow the formal presentation.

Unknown Executive: Question and Answer Session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded.

Anyone should require operator assistance during the conference. Please press star zero on your telephone keypad.

As a reminder, this conference is being recorded.

Raymond Furey: It is now my pleasure to introduce our first speaker, Ray Furey. Rigel's Executive Vice President, General Counsel, and Corporate Secretary.

Speaker Change: It is now my pleasure to introduce our first speaker Rafe theory right.

Mr. Ferry: Fragile executive Vice President General Counsel and corporate Secretary. Thank you. Mr. Ferry you may begin.

Raymond Furey: Thank you, Mr. Furey. Welcome to our fourth quarter of full year 2024 financial results and business update conference call. The financial press release for the fourth quarter of the full year 2024 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 made 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 forecast.

Welcome to our fourth quarter and full year 2024 financial results and business update conference call.

Mr. Ferry: The financial press release for the fourth quarter and full year of 2024 was issued a short while ago can be.

Mr. Ferry: Be viewed along with the slides for this presentation and the news and events section of our Investor Relations site.

Mr. Ferry: As a reminder, during today's call we may make.

Mr. Ferry: Forward looking statements regarding our financial outlook and our plans.

Mr. Ferry: Timing regulatory and product development.

Mr. Ferry: These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

Raymond Furey: The description of these risks can be found on our most recent annual report on Form 10-K for the year ended December 31st, 2024 on file with the SEC.

Mr. Ferry: A description of these risks can be found on our most recent annual report on Form 10-K for the year ended December 31 2024.

Mr. Ferry: Sir.

Raymond Furey: Any forward-looking statements are made as of today's date only and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances.

Mr. Ferry: Any forward looking statements are made as of today's date, only and we undertake no obligation to update these forward looking statements.

Mr. Ferry: Congrats for sure.

Raul Rodriguez: At this time, I'd like to turn the call over to our president, Chief Executive Officer Raul Rodriguez-Ferrado. Thank you, Ray, and thank you, everyone, for joining 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.

Speaker Change: At this time I would like to turn the call over to our President and Chief Executive Officer.

Mr. Ferry: Problems.

Ray: Thank you Ray and thank you everyone for joining today also.

Ray: Also with me today are David Santos, our Chief Commercial officer, Mr. Roy Carroll, our Chief Medical Officer, and being shortened our Chief Financial Officer.

Raul Rodriguez: Beginning on slide four, we will provide an overview of Rigel's business and our numerous accomplishments in 2024. For those that are new to the company, let me take a moment to review Rigel's overall corporate strategy to grow our hematology and oncology business. Our strategy is focused on three main goals. First, expand our commercial portfolio and increasing product sales. Second, advancing and growing our pipeline through internal development and strategic collaboration.

Ray: Beginning on slide four where we will provide an overview of rifles business and our numerous accomplishments in 2024.

Ray: For those that are new to the company, let me take a moment to review right on the overall corporate strategy to grow our hematology and oncology business.

Ray: Our strategy is focused on three main goals first expand our commercial portfolio and increasing product sales.

Ray: Advancing and growing our pipeline through internal development and strategic collaborations and third maintaining financial discipline.

Raul Rodriguez: and third, maintaining financial 2024 was a transformational year for Rigel. As we delivered on all three of these goals, I will take you through each of these accomplishments in more detail. In 2024, we set another record year of sales. As a result of our effective commercial execution, we reached our highest commercial portfolio sales ever at 145 million. 39% growth over 2023. The significant revenue growth was driven by the strength of Tavalisse and Resiladia sales and the addition of Gavreto, our third product, and our second in licensed product, which contributed $17.1 million in net product sales since we added it to our portfolio in June.

Ray: 2024 was a transformational year for Rigel as we delivered on all three of these goals I won't take you through each of these accomplishments in more detail.

Ray: In 2024, we set another record year of sales.

Ray: As a result of our effective commercial execution, we reached our highest commercial portfolio cells ever at 145 million.

Ray: 39% growth over 2023.

Ray: The significant revenue growth was driven by the strength of tower lease Enbridge Lady in sales and the addition of Red Oak, our third product in our circuit did licensed product, which contributed $17 1 million in net product sales since we added to our portfolio in June.

Raul Rodriguez: We also generated revenues from our partners where Tavalisse is commercially available. And our partners continue to make progress towards expanding Tavalisse access in other geographies. Recently, NITE and KISE announced regulatory approvals for Tavalis in two new countries, Mexico and the Republic of Korea, respectively.

Ray: We also generated revenues from our partners were top of leases commercially available.

Ray: And our partners continue to make progress towards expanding type of lease access in other geographies.

Speaker Change: Certainly Knight and T. J I know its regulatory approvals for tower leasing two new countries, Mexico, and the Republic of Korea, respectively.

Raul Rodriguez: Once commercially launched, ITP patients in these countries can also benefit from Tavalis.

Speaker Change: Once commercially launch I T P patients in these countries can also benefit from travelers.

Raul Rodriguez: For RISLINIA, we actively pursued new collaborations and executed new license agreements with our partner Kesey in three countries in Asia and with Dr. Reddy for numerous territories outside of the U.S.

Speaker Change: Orbis linear we actively pursue new collaborations and executed new license agreements with our partner Chiesi in three countries in Asia and with Dr. Reddy for numerous territories outside of the U S.

Raul Rodriguez: Also in 2024, on our second goal, we made significant progress in our development pipeline. We continue to evaluate R289, our dual IRAC1 and IV inhibitor, in an ongoing Phase 1b study in patients with lower risk MDS. We presented encouraging initial safety and efficacy data from that study at the ASH annual meeting in December. Enrollment in the dose escalation portion of the trial, where we recently completed the fifth dose level, and have now opened for enrollment a new sixth dose level at 500 milligrams BID. For eludasidinib, our strategic collaborations with MD Anderson and Connect organization continue to progress.

Speaker Change: Also in 2024 on our second goal, we made significant progress in our development pipeline.

Speaker Change: We continue to evaluate our to our to ignite our dual Iraq, one and four inhibitor and an ongoing phase one b study in patients with lower risk Mds.

Speaker Change: We presented encouraging initial safety and efficacy data.

Speaker Change: From that study at the Ash annual meeting in December.

Speaker Change: Enrollment in the dose escalation portion of the trial, where we recently completed the fifth dose level.

Speaker Change: And they have now opened for enrollment or new six dose level at 500 milligrams B I D.

Progress in our strategic collaborations with M D Anderson and connect organization continue to progress. These trials will provide us with the opportunity to explore a lunar sitting up in a range of I D. H, one mutant cancers, and a time and cost efficient manner.

Raul Rodriguez: These trials provide us with the opportunity to explore eludasidinib in a range of IDH1 mutant cancers in a time and cost efficient manner. We're excited to report that all four studies from our multi-year strategic development alliance with MD Anderson have now opened for enrollment. And the Phase II study of Olucidinib and high-grade glioma in collaboration with CONNECT has also recently opened for enrollment.

Speaker Change: Cited to report that all four studies from our multiyear strategic development Alliance with MD Anderson have now opened for enrollment in the phase II study of obesity and high grade Glioma and collaboration with connect has also recently opened for enrollment.

Lisa Rojkjaer: Lisa will provide you an update on these development programs in a few minutes.

Speaker Change: Lisa will provide you an update on these development programs in a few minutes.

Raul Rodriguez: And lastly, in 2024, on our third goal, maintaining financial discipline, by maintaining financial discipline, we were able to for the first time generate full year net income of 17 million dollars. and our cash balance increased by more than $20 million for the year. All of these accomplishments enable Rigel to continue to successfully implement our strategy.

Speaker Change: And lastly in 2024 on our third goal maintaining financial discipline, while maintaining financial discipline, we were able to for the first time.

Speaker Change: Generate full year net income of $17 million.

Speaker Change: And our cash balance increased by more than 20 million for the year.

Speaker Change: All of these accomplishments enabled rigel to continue to successfully implement our strategy.

Raul Rodriguez: Moving on to the next slide. We have continued to grow our net product sales over time, with a compound annual growth rate of 32%. up from between 2021 and 2024. Tavalis grew nicely over that period, and the addition of Rizlydia in late 22 and Gavreto in 2024 has provided additional contributions to that growth. All three of these products achieved new highs in 2024. And in 2025, as you can see on slide six, we're expecting approximately $145 million to $192 million in net product sales for the year. Approximately a 28 to 32% growth compared to 2024.

Speaker Change: Moving on to the next slide.

Speaker Change: We have continued to grow our net product sales overtime with a compound annual growth rate of 32%.

Speaker Change: Between 2021, and 2024 type of lease grew nicely over that period and the addition of bridges linear in late 'twenty, two and get Red Oak. In 2024 has provided additional contributions to that growth. All three of these products achieved new highs in 2024.

Speaker Change: And then 2025 as you can see on slide six we're expecting approximately 145 million to 192 million and net product sales for the year.

Speaker Change: Approximately 28% to 32% growth compared to 2024.

Raul Rodriguez: So just to summarize, 2024 was a transformational year where we continue to grow our hematology and oncology business while at the same time becoming a profitable company.

Speaker Change: So just to summarize 2024, it was a transformational year, where we continued to grow our hematology and oncology business, while at the same time, becoming a profitable company.

David Santos: And with that, I'll turn the call over to Dave to provide a commercial update. Dave? Thank you, Raul. On slide 8, you'll see our three commercial products, Tabaliz, Reslydia, and GetReady. We are very pleased with the strong growth in revenues in the fourth quarter and full year 2024. Moving to slide nine, you see how our quarterly and annual sales have evolved since 2021. We've grown each quarter's sales over the previous year, and that growth continues, particularly from last year to this year. We started the first quarter of 2023 with $23.8 million and are now reporting $46.5 million for the fourth quarter of 2024.

Dave: And with that I'll turn the call over to Dave to provide a commercial update.

Dave: Thank you Raul.

Dave: On slide eight you'll see our three commercial products, probably spreads lady yet and spread out.

Speaker Change: We are very pleased with the strong growth in revenues in the fourth quarter and full year in 2024.

Speaker Change: Moving to slide nine you see how our quarterly and annual sales have evolved since 2020, what we've grown each quarter sales over the previous year and that growth continues particularly from last year to this year. We started the first quarter of 2023 with $23 $8 million and are now reporting.

Speaker Change: $46 $5 million for the fourth quarter of 2024.

David Santos: That growth has been driven by our strong commercial execution in consistently building quarterly demand for Taboliz and driving broader awareness of Reslydia through the first two years of its launch. In addition, our ability to successfully and seamlessly transition Gabretto into our portfolio has significantly expanded our top lot. Compared to the fourth quarter of 2023, we generated 58% growth in the fourth quarter of 2024. For full year 2024, we delivered record revenues of nearly $145 million, an increase of $41 million or 39% compared to 2023 net sales of $104 million. Our commercial team has been dedicated to execution, driving continued momentum for Tavalese and improving both institutional and community demand for ResLydia, and successfully transitioning Gevretto patients and accounts to Rigel labeled products.

Speaker Change: That growth has been driven by our strong commercial execution and consistently building quarterly demand for top lease and driving broader awareness of <unk> through the first two years of its launch.

Speaker Change: In addition, our ability to successfully and seamlessly transition got bread out into our portfolio has significantly expanded our top line.

Speaker Change: Compared to the fourth quarter of 2023, we generated 58% growth in the fourth quarter of 2024.

Speaker Change: For full year 2024, we delivered record revenues of nearly 145 million, an increase of $41 million or 39% compared to 2023 net sales of 104 million. Our commercial team has been dedicated to execution driving continued momentum for <unk>.

Speaker Change: He's an improving both institutional and community demand for S. Libya and successfully transitioning give rental patients and accounts to rigel labeled product my sincere. Thanks to the entire team for all their hard work to grow our business in 2024.

David Santos: My sincere thanks to the entire team for all their hard work to grow our business in 2020.

David Santos: Slide 10 shows a summary of our commercial performance by product. First on Tavolis, I'm pleased to report another strong quarter in which we generated $31 million in net product sales, an increase of 21% compared to the fourth quarter of 2023. This growth was driven by strong patient demand with another consecutive quarterly record high. We continue to grow Tavaleze's demand through both refills for patients who stay on the product and new prescriptions for patients who are starting Tavaleze for the first time. Moving to Reslydia, we reported $7.4 million in net product sales, almost doubling revenue from the prior year period as we focus on improving Reslydia adoption, both in institutions and the community, by raising awareness of Reslydia's efficacy, particularly in patients who have failed upfront therapy with Minoxidil.

Speaker Change: Slide 10 shows a summary of our commercial performance by product first on top of lease I'm pleased to report another strong quarter in which we generated $31 million and net product sales an increase of 21% compared to the fourth quarter of 2023.

Speaker Change: This growth was driven by strong patient demand with another consecutive quarterly record high we continue to grow top of lease demand through both refills for patients who stay on the product and new prescriptions for patients who are starting top at least for the first time.

Speaker Change: Moving the rest linear we reported $7.4 million and net product sales almost doubling revenue from the prior year period, as we focus on improving rez linear adoption both in institutions and the community by raising awareness of rents Lady is efficacy, particularly impatient.

Speaker Change: Two failed upfront therapy with black box.

David Santos: And lastly, for Gavretto, in our second full quarter selling the product, we delivered $8.1 million in net product sales in Q4. We are very happy with the success in transitioning over Gavreto patients, prescribers, and accounts to Rigel's distribution network. Importantly, our $8.1 million of net product sales in the fourth quarter represent a run rate above the $28 million in annual sales of Gavreto in 2023 under prior ownership. We are especially pleased with Givretto's upward trajectory during last year's transition and are now focused on building on that momentum in 2025.

Speaker Change: And lastly, forget read out in our second full quarter selling the product, we delivered $8 $1 million and net product sales in Q4.

Speaker Change: We are very happy with the success in transitioning over to Red Oak patients prescribers and accounts to Rigel distribution network importantly, our $8.1 billion of net product sales in the fourth quarter represent a run rate above the $28 million in annual sales of gift Gretel in 'twenty.

Speaker Change: 23 under prior ownership.

Speaker Change: We are especially pleased with give rados upward trajectory during last year's transition and are now focused on building on that momentum in 2025.

David Santos: Moving to slide 11, we hit several meaningful milestones with our portfolio in 2024. Importantly for Tavalis, 2024 was the first year to achieve more than $100 million in net sales. It continues to grow steadily as the foundation of our portfolio. consistently hitting new record quarterly highs in bottle ship to patients. That steady growth has been driven by more new patients starting on tablilis each quarter and the subsequent increased carryover that's generated. in 2025, we expect that trend to continue. Reslydia more than doubled both bottle ship to patients in clinics, as well as net sales in 2024.

Speaker Change: Moving to slide 11, we had several meaningful milestones with our portfolio in 2024 importantly for top of lease 2024 was the first year to achieve more than $100 million in net sales. It continues to grow steadily as the foundation of our portfolio.

Speaker Change: Consistently hitting new record quarterly highs in bottles shipped to patients and clinics.

That steady growth has been driven by more new patients starting on top of lease each quarter and the subsequent increase carryover that's generated.

Speaker Change: In 2025, we expect that trend to continue.

Speaker Change: But its linear more than doubled our bottles shipped to patients and clinics as well as net sales in 2024, and we believe we still have significant opportunity to grow rents, but he is used in mutant IV H, one relapsed or refractory acute myeloid leukemia.

David Santos: And we believe we still have significant opportunity to grow Reslydia's use in mutant IDH1 relapsed to refractory acute myeloid leukemia. We continue to find that as clinicians become more aware of Reslydia's efficacy in post-venetoclax patients, they believe it's clinically meaningful, as these patients are very difficult to treat with other therapies. We believe we can build on the scientific data currently available in this important population of AML patients and continue to grow ResLydia's use in 2025.

Speaker Change: We continue to fight that as clinicians become more aware of wrestling. He has efficacy in post spin out of class patients. They believe it's clinically meaningful as these patients are very difficult to treat with other therapies.

Speaker Change: We believe we can build on the scientific data currently available in this important population of AML patients and continue to grow rents really has us in 2025.

David Santos: Lastly, in 2024, our successful transition of Gevretto demonstrates our nimble and highly adaptable organizational capability. We fully leveraged our commercial and medical affairs infrastructure and expertise to meaningfully expand our hematology and oncology portfolio and quickly generated $17.1 million of incremental net sales in 2024. The Q4-Devretto net sales result of $8.1 million reinforces how smoothly and effectively both new and existing patients were transitioned. And furthermore, the fact that we were also able to significantly grow Tavalese and Reslydia while that transition was ongoing is a testament to our organizational capabilities and operational establishment. In 2025, we can continue to grow Gevretto, particularly since the use of RET inhibitors in non-small cell lung cancer should continue to expand in the frontline city.

Speaker Change: Lastly in 2024, our successful transition of give red oak's demonstrates our nimble and highly adaptable organizational capabilities, we fully leveraged our commercial and medical affairs infrastructure and expertise to meaningfully expand our hematology and oncology portfolio.

Speaker Change: And quickly generated $17.1 million of incremental net sales in 2024.

Speaker Change: The Q4 give Reno net sales result of $8 $1 million reinforces how smoothly and effectively both new and existing patients were transitioned and Furthermore, the fact that we were also able to significantly grow top of lease had rents Lydia while that transition was on.

Speaker Change: Going is it a testament to our organizational capabilities and operational efficiency.

Speaker Change: In 2025, we can continue to grow caporetto, particularly since the use of ret inhibitors in non small cell lung cancer should continue to expand in the frontline setting.

David Santos: New non-small cell lung cancer treatment guidelines released by the National Comprehensive Cancer Network, or NCCN, in January now recommend that if a RET inhibitor was not used in the frontline setting, clinicians may switch frontline therapy to a RET inhibitor once the RET fusion is confirmed. We believe that RET inhibitor use will expand in non-small cell lung cancer in 2025 and beyond, and Gibretto will grow.

Speaker Change: New non small cell lung cancer treatment guidelines released by the National comprehensive cancer network or N C. C N in January.

Speaker Change: Now recommend that if a ret inhibitor was not used in the frontline setting clinicians may switch frontline therapy to our ret inhibitor once the ret fusion is confirmed.

Speaker Change: We believe that ret inhibitor use will expand in non small cell lung cancer in 2025, and beyond and give red it will grow in turn.

David Santos: Finally, moving to slide 12, we're incredibly excited about our work to expand access to our patients in markets outside of For more information visit www.FarzinHaque.com Tavalis is commercially available in Japan, in Europe under the brand name Tavales, and in Canada and Israel via our partners Kiese, Grifols, and Medisoc, and that's generating sustainable revenues each quarter. In addition, our partners continue to pursue regulatory approvals for Tavalis in new markets. As Raul mentioned, Knight Therapeutics announced it has received regulatory approval for Tavalese in Mexico, and recently, Quise announced regulatory approval for Tavalese in Korea. In 2024, we also look to find partners to develop and commercialize Reslydia in ex-U.S.

Speaker Change: Finally, moving to slide 12, we're incredibly excited about our work to expand access to our patients in markets outside of the U S. How beliefs is commercially available in Japan in Europe under the brand name type of less and in Canada, and Israel be our partners he say cripples edmar.

Speaker Change: Scott and that's generating sustainable revenues each quarter.

Speaker Change: In addition, our partners continue to pursue regulatory approvals for tower leasing new markets as Ralph mentioned Knight Therapeutics announced it has received regulatory approval for <unk> in Mexico, and recently, he say announced regulatory approval for <unk> in Korea.

Speaker Change: In 2024, we also look to find partners to develop and commercialize rests linear in ex U S markets. We expanded our relationship with key say to include Japan, Korea, and Taiwan Forensically, yet in all potential indications and in late 'twenty 'twenty four we entered into an exclusive.

David Santos: We expanded our relationship with KISAI to include Japan, Korea, and Taiwan for Reslydia in all potential indications. And in late 2024, we entered into an exclusive license agreement with Dr. Reddy's for Reslydia in all potential indications throughout Dr. Reddy's. which includes Latin America and others. We are pleased that access to our products is expanding outside the U.S., and we continue to explore other opportunities for partnerships outside the U.S. to bring our products to other markets and patients around the globe.

Since agreement with Doctor Readies for rents Lady and all potential indications throughout Doctor Readies territory, which includes Latin America and other territories.

Speaker Change: We are pleased that access to our products is expanding outside the U S and we continue to explore other opportunities for partnerships outside the U S to bring our products to other markets and patients around the globe I will now pass the call over to Lisa to provide an update on our development pipeline Lisa.

Lisa Rojkjaer: I will now pass the call over to Lisa to provide an update on our development pipeline. Lisa? Thanks, Dave. We made meaningful progress in 2024 and look forward to continued execution on our strategy to expand our hematology and oncology portfolio in 2025.

Speaker Change: Yeah.

Lisa: Thanks, David we made meaningful progress in 'twenty 'twenty, four and look forward to continued execution on our strategy to expand our hematology and oncology portfolio in 2025.

Lisa Rojkjaer: I'm on slide 14. First, from our development pipeline, R289 is our novel dual IRAC1 and IV inhibitor that is currently being evaluated in a phase 1B study in patients with relapsed refractory lower-risk myelodysplastic syndrome, or MDS. We're excited that R289 has been granted both fast-track designation for the treatment of patients with previously treated transfusion-dependent lower-risk MDS and orphan drug designation for MDS by the FDA. Furthermore, as part of Rigel-sponsored development programs, and alongside our partners, MD Anderson and the Connect Cancer Consortium, elutacidinib is being evaluated in new indications. We believe elutacidinib 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.

Speaker Change: I'm on slide 14.

Speaker Change: First from our development pipeline Archie right now and that's our novel dual Iraq. One four inhibitor that is currently being evaluated in a phase one b study in patients with relapsed refractory <unk> lower risk Myelodysplastic syndrome, or Mds, we're excited that arent too late night and has been granted both fast track designation for the treatment of pace.

Speaker Change: Since with previously treated in transfusion dependent lower risk Mds and orphan drug designation for M. D. S. I D. S T a.

Speaker Change: Furthermore, as part of Rigel sponsored development programs and alongside our partners M. D. Anderson and the connects cancer consortia Alicia sitting there that's being evaluated in new indications. We believe the Elisa Sydney has potential in several cancers, where mutated I D. H one plays a role such as glaucoma.

Speaker Change: All AML segments and M D S either as monotherapy or in combination we expect to initiate a rigel sponsored phase two study to evaluate alimta sitting up in her correctly in 2025. In addition, that's right I'll mention all four clinical trials under our MD Anderson collaboration are now open for enrollment.

Lisa Rojkjaer: We expect to initiate a Rigel-sponsored Phase II study to evaluate elutacidinib in recurrent glioma in 2025. In addition, as Raul mentioned, all four clinical trials under our MD Anderson collaboration are now open for enrollment, as is the Connect study focused on high-grade glioma.

Speaker Change: Element adds as the connect studies focused on high grade glioma.

Lisa Rojkjaer: We also remain focused on evaluating potential opportunities to in-license or acquire products that would be a strategic fit for our portfolio. We're looking for differentiated products in hematology, oncology, or related areas. Products that are late stage, possibly with registrational data, soon to have registrational data, or more advanced. And products that can leverage our hematology and oncology infrastructure. As demonstrated with our acquisitions of AlutaSetnib and ProSetnib, our goal is to continue to find assets that align with our organization, pipeline, and ability to execute.

Speaker Change: We also remain focused on evaluating potential opportunities to in license or acquire products that would be a strategic fit for our portfolio. We're looking for differentiated products in hematology and oncology or related areas product set or late stage, possibly with Registrational data soon to have registrational data.

Speaker Change: Our more advanced products that can leverage our hematology and oncology infrastructure.

As demonstrated with our acquisitions of Alicia sitting up in pro setting up our goal is to continue to find assets that align with our organization pipeline and ability to execute.

Lisa Rojkjaer: Now we'll spend a few moments discussing the updates from our R289 program. To help frame the discussion, slide 16 presents an overview of the value proposition of R289 and lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the U.S. Recent development efforts in lower-risk MDS have focused primarily on first-line therapies. However, there's a high unmet need for next-line therapies, particularly for previously treated transfusion-dependent patients. This regulation of inflammatory signaling is key to the pathogenesis of lower-risk MDS, and IROC 1 and 4 mediate this process. Blocking both IRAC1 and IV may suppress marrow inflammation and leukemic stem and progenitor cell function and restore hematopoiesis.

Speaker Change: Now I'll spend a few moments discussing the updates from our our 289 program.

Speaker Change: To help frame the discussion slide 16 prevents presents an overview of the value proposition of our 289 in lower risk Mds thereabout.

Speaker Change: There are about 12000 previously treated lower risk Mds patients in the U S. Recent development efforts in lower risk Mds have focused primarily on first line therapies. However, there's a high unmet need for next line therapy, particularly for previously treated transfusion dependent patients.

Speaker Change: This regulation of inflammatory signaling is key to the pathogenesis of lower risk Mds and Iraq, one and four mediate this process block.

Speaker Change: Blocking both Iraq, one in four may suppress Maryland, inflammation, and leukemic stem and progenitor cell function and restore hematopoiesis.

Dean Schorno: R835, the active moiety of R289, blocks TOA-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 LTS-induced cytokine release compared to placebo. As a reminder, R289, which is currently being evaluated in the clinic, is the oral pro-drug that is rapidly converted to R835 in the gut. R289 has both FDA fast-track and orphan drug designations, giving the molecule an expedited regulatory pathway, potential priority review, and seven years of market exclusivity upon approval.

Speaker Change: Our 835, the active moiety of art to eight nine blocks toll like receptor and IL one receptor signaling in vitro and was active in various preclinical models of inflammation clinic.

Clinical proof of concept that this anti inflammatory effects came from a healthy volunteer study in which our 835 markedly suppressed L. P. S induced cytokine release compared to placebo.

Speaker Change: As a reminder, arent to eight nine which is currently being evaluated in the clinic is the oral pro drugs that is rapidly converted to our a street fight and looked at.

Speaker Change: Our 289 has suppose S T a fast track and orphan drug designations, giving the molecule an expedited regulatory pathway potential priority review and seven years of market exclusivity upon approval.

Dean Schorno: 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 1b study. The initial dose escalation data that were recently presented at the ASH annual meeting will be reviewed on today's call. Slide 17, you see the treatment landscape for lower risk MDS. MDS is a clonal disorder of hematopoietic stem cells leading to dysplasia and an effect of hematopoiesis. The main consequences for patients are anemia and transfusion dependence, which adversely impact their quality of life.

Speaker Change: Both of these designations underscore the agencies interest in this rare disease and their willingness to collaborate with Rachel and the development of our 289.

Speaker Change: In addition, our 289 months, thus far demonstrated a promising preliminary clinical profile in a phase <unk> study initial.

Speaker Change: The initial dose escalation data that were recently presented at the Ash annual meeting will be reviewed on todays call.

Speaker Change: On slide 17, you see the treatment landscape for lower risk Mds M.

Speaker Change: M D S. As a clonal disorder of hematopoietic stem cells, leading to dysplasia, and then effective Hawaii and other places.

Speaker Change: The main consequences for patients, our anemia, and transfusion dependence, which adversely impact their quality of life.

Dean Schorno: 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 lispatercept. A metal stat was approved earlier this year for ESA failure high transfusion burden, lower risk MDS. With eight-week transfusion independence rates approaching 40% with mootless pattercept and the metal stat, 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.

Speaker Change: In addition infections iron overload from transfusions, and subsequent organ dysfunction, all negatively impact the patient.

Speaker Change: Slide from transfusions initial therapies include erythropoiesis stimulating agents or Esa as patients are eligible and this pattern.

Speaker Change: And that'll start was approved earlier this year for Esa failure high transfusion burden lower risk Mds.

Speaker Change: With eight week transfusion independence rates approaching 40%, what's the pattern stepped in the metals that many patients require an alternative treatment option.

Speaker Change: Oh, hyperventilating agents or hma's or improve the percentage of patients achieving transfusion independence is low.

Speaker Change: Therefore, there is a high unmet need for safe effective treatment options following failure with approved therapies, particularly for previously treated transfusion dependent patients.

Dean Schorno: On slide 18, you'll see the design of our ongoing open-label dose-escalation, dose-expansion Phase 1b study in relapsed refractory lower-risk MDF patients with either symptomatic anemia or transfusion dependence. The study was recently updated to include a sixth dose level, 500 mg BID, and to facilitate the randomized comparison of two dose levels and expansion to optimize selection of the recommended phase 2 dose. The primary endpoints are safety and selection of the recommended dose for expansion, and secondary endpoints include transfusion independence, hemologic improvement, response rates, and The study continues to progress well, with the 6th dose level of 500mg BID now open for enrollment.

Speaker Change: On slide 18, you'll see the design of our ongoing open label dose escalation dose expansion phase one b study in relapsed refractory lower risk Mds patients with either symptomatic anemia or transfusion dependence.

Speaker Change: The study was recently updated to include the sixth dose level 500 milligrams B I D and to facilitate the randomized comparison of two dose levels and expansion to optimize selection of the recommended phase two dose.

Speaker Change: The primary endpoints are safety and selection of the recommended dose for expansion.

Speaker Change: Secondary endpoints include transfusion independence, hematologic improvement response rates and P. K.

The study continues to progress well with the sixth dose level 500 milligrams PID now open for enrollment.

Dean Schorno: Once the recommended Phase 2 dose has been determined, an exploratory cohort of first-line lower-risk MDS patients will be open to evaluate R289 in an earlier line of therapy.

Speaker Change: Once the recommended phase two dose has been determined an exploratory cohort of first line lower risk Mds patients will be open to evaluate our 289 in an earlier line of therapy.

Dean Schorno: Now I'd like to walk you through the initial dose escalation data that were recently presented at the ASH annual meeting. On slide 19, we start with patient characteristics. Data on 22 patients were reported using an October 25, 2024 data cutoff date. The median age was 76, and about 60% of the patients were age 75 or above. The median number of prior therapies was three, ranging from one up to eight, and more than 70% of patients had received an HMA or leucopterase. The majority of patients, 73%, were high transfusion burden at baseline. The median time on therapy was 4.6 months.

Speaker Change: Now I'd like to walk you through the initial dose escalation data that were recently presented at the Ash annual meeting.

Speaker Change: On slide 19, we start with patient characteristics.

Speaker Change: Data on 22 patients were reported you're saying on October 22024 data cutoff date.

Speaker Change: D and age was 76 and about 60% of the patients were aged 75 or above.

Speaker Change: The median number of prior therapies was treat ranging from one to eight and more than 70% of the patients had received an HMA or at least Patterson.

Speaker Change: The majority of patients, 73% were high transfusion burden at baseline.

Speaker Change: The median time on therapy was 4.6 months in summary, these are elderly heavily pre treated patients with a high transfusion burden at baseline.

Dean Schorno: In summary, these were elderly, heavily pre-treated patients with a high transfusion burden at baseline.

Dean Schorno: Moving to slide 20, we'll review the safety findings. R289 was generally well tolerated. The most common treatment emergent adverse events in 20% or more patients, which are not shown on the slide, were diarrhea and fatigue, followed by chills, nausea, and pruritus, all of which were grade 1 or 2. The most frequent grade 3 or 4 adverse events with two events each were anemia, platelet count decreased, pneumonia, and alanine aminotransferase, or ALT. The treatment-related adverse events are shown on the slide. Importantly for this patient population, the incidence of grade 3-4 cytopenias and infections was low. There was one dose-limiting toxicity reported, a grade 3-4 transaminase increase in one patient at the 750 mg daily dose level.

Speaker Change: Moving to slide 'twenty well review the safety findings are 289 was generally well tolerated. The most common treatment emergent adverse events in 20% or more patients, which are not shown on the slide where diarrhea, and fatigue, followed by chills, nausea, and pruritus all of which were grade one or two.

Speaker Change: The most frequent grade three or four adverse events with two events, each where anemia platelet count decreased pneumonia and alanine aminotransferase or a L. T increased.

Speaker Change: The treatment related adverse events are shown on the slide.

Speaker Change: Importantly for this patient population.

So that's a great three foreign cytopenia as in infections was low.

Speaker Change: There was one dose limiting toxicity reported a grade three four transaminase increase and one patient at 750 milligram daily dose level.

Dean Schorno: Serious adverse events occurring in two or more patients were pneumonia and upper GI bleed. Both occurred in two patients each and were unrelated to therapy.

Speaker Change: The adverse events occurring in two or more patients where pneumonia that upper Gi bleed both occurred in two patients each and were unrelated to therapy.

Dean Schorno: In slide 21, we show the preliminary efficacy data.

Speaker Change: On slide 21, we show the preliminary efficacy data and.

Dean Schorno: The swimmer plot shows each patient and the red cell transfusions by dose group, starting with the lowest dose group, 250 mg daily, on top. Per the IWG 2018 criteria, the transfusion history for each patient was collected for 16 weeks prior to our 289 administration to establish the baseline transfusion frequency. shown to the left of day zero indicated by the red arrow. Two patients, numbers 9 and 19, were not transfusion-dependent at baseline. Eighteen patients were valuable for efficacy, meaning that they had one or more R289 doses and at least one efficacy assessment. Red blood cell transfusion independence lasting 8 weeks or longer was achieved by 3 patients, one receiving 500mg daily and two receiving 750mg daily.

Speaker Change: The swimmer plot shows each patient in the Red cell transfusions by dose group, starting with the lowest dose groups 250 milligrams daily on top.

Speaker Change: Or the IEE achieve 2018 criteria and transfusion history for each patient was collected for 16 weeks prior to our 289 administration to establish the baseline transfusion frequency shown to the left of days zero indicated by the Red Arrow.

Speaker Change: Two patient numbers nine or 19, we're not transfusion dependent at baseline.

Speaker Change: 18 patients were evaluable for efficacy, meaning that they had one or more of our 289 doses and at least one efficacy assessment right.

Speaker Change: Red blood cell transfusion independents, lasting eight weeks or longer wasn't cheap by three patients one receiving 500 milligrams daily and to receiving 750 milligrams daily.

Dean Schorno: In two patients, RBC transfusion independence lasted for more than six months. and one patient also achieved a marrow complete response. The median duration of transfusion independence was 29 weeks. One high-transfusion burden patient receiving 500 mg daily achieved a minor HIE response with a 64% reduction in red blood cell transfusions compared to baseline. Regarding PK, at doses at or higher than 500 milligrams once daily, RA35 plasma concentrations reached or exceeded those associated with 50% or 90% LPS-induced cytokine inhibition that was previously observed in healthy volunteers. We thought it was interesting that at these doses, hemologic responses occurred in 4 out of 10, or 40% of the valuable transfusion-dependent patients.

Speaker Change: And two patients RBC transfusion independence lasted for more than six months.

Speaker Change: And one patient also choose to marrow complete response.

The median duration of transfusion independence was 29 weeks.

Speaker Change: One the high transfusion burden patients receiving 500 milligrams daily achieved a minor HIV response, with a 64% reduction in red blood cell transfusions compared to baseline.

Speaker Change: Regarding PK doses at or higher than 500 milligrams once daily or three five plasma concentrations reached or exceeded those associated with 50% or 90% L. P. S induced cytokine inhibition that was previously observed in healthy volunteers.

Speaker Change: We thought it was interesting that these doses hematologic responses occurred in four out of 10 or 40% of the valuable transfusion dependent patients.

Dean Schorno: On slide 22, we see a summary of the responding patients. The majority were high transfusion burden at baseline and had received a variety of prior therapies, including Lispatercept, hypomethylating agents, and some experimental therapies. The two patients with durable transfusion independence lasting more than 6 months, patients 4 and 10, were both high transfusion burden at baseline and had received HMAs. Beneath the table are the hemoglobin levels over time for the three patients that achieve 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.

Speaker Change: On slide 22, we see a summary of the responding patients. The majority were high transfusion burden at baseline had received a variety of prior therapies, including with Patterson I pulled alkylating agents and some experimental therapies the.

Speaker Change: The two patients with durable transfusion independence lasting more than six months patients four and 10 were both high transfusion burden at baseline and had received hma's.

Speaker Change: The NESA table are the hemoglobin levels over time for the three patients that achieved transfusion independence.

Speaker Change: Hemoglobin increases ranging from 2.3 to five six grams per deciliter compared to baseline or observed indicating that our 289 has the potential to correct anemia, providing support for its evaluation earlier in treatment.

Dean Schorno: In summary, the initial data is encouraging, showing R289 is generally well-tolerated with promising signs of efficacy in heavily pre-treated transfusion-dependent patients.

Speaker Change: In summary, the initial data is encouraging showing our 289 is generally well tolerated with promising signs of efficacy in heavily pretreated transfusion dependent patients.

Lisa Rojkjaer: Now I'll shift focus to elucasidinib, our IDH1 inhibitor.

Speaker Change: Now, we'll shift focus to a looser sitting at our I D. H one inhibitors.

Lisa Rojkjaer: Beginning on slide 24, glioma is an area that is incredibly challenging where there has 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 in up to almost 40% of younger patients. Unfortunately, most disease recurs and there is no standard of care therapy for relapsed patients. The recent approval of voracitinib, an IDH 1 and 2 inhibitor in grade 2 gliomas, has highlighted the potential for IDH inhibitors in gliomas.

Speaker Change: Beginning on slide 24, we all know it's an area that is incredibly challenging where theres not been much advancement of therapeutic options.

Speaker Change: The physical elements of the most common primary brain tumor in adults affecting approximately 20000 in the U S. Each year.

Speaker Change: I D. H, one mutations occur in about 70% of patients with grade two and three and are found at up to almost 40% of younger patients.

Speaker Change: Unfortunately, most disease recurs and there is no standard of care therapy for relapsed patients.

Speaker Change: The recent approval of Forest City, and I think each one and two inhibitor and grades and grade simply Armours has highlighted the potential Friday H inhibitors.

Lisa Rojkjaer: Elutocidinib was previously evaluated in a Phase 1B2 study in 26 patients, which was published in the journal Neuro-Oncology. Two patients with high-grade glioma achieved partial responses. Both had enhancing tumors. And 10 patients achieved stable disease for a disease control rate of 48%. This clinical proof of concept supports further evaluation of elutocidinib and glioma.

Speaker Change: Alicia sit in our books previously evaluated in a phase <unk> study in 26 patients, which was published in the journal of Neuro oncology.

Speaker Change: Patients with high grade glioma achieved partial responses both had enhancing tumors.

Speaker Change: 10 patients achieved stable disease for a disease control rate of 48%.

Speaker Change: This clinical proof of concept supports further evaluation of a leukocyte and they've been glioma.

Lisa Rojkjaer: Moving to slide 25.

Speaker Change: Moving to slide 25 last year, we entered a collaboration with the global Neuro oncology consortium connect.

Lisa Rojkjaer: Last year, we entered a collaboration with the Global Neuro-Oncology Consortium, CNET. InConnect'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 elutocidinib in combination with temozolomide, followed by elutocidinib monotherapy in newly diagnosed patients between 12 and 39 years of age with IDH1 mutation-positive high-grade glioma. This study was recently opened for enrollment.

Speaker Change: And then next target trial, a molecularly guided phase two umbrella clinical trials for high grade Gliomas. The Rigel sponsored study target D well evaluate a post radiotherapy maintenance regimen of a looser sitting up in combination with tennis dolomite, followed by a leukocyte mono therapy in newly diagnosed.

Speaker Change: Most patients between 12, and 39 years of age beside each one mutation positive high grades.

Speaker Change: This study was recently opened for enrollment.

Lisa Rojkjaer: In addition, we recently announced that this year we plan to initiate a Phase II clinical study in recurrent glioma and we look forward to providing more details about that study later this year. We think this is an important opportunity as there is a significant unmet medical need in this patient population. We, along with CONNECT, are excited about elutacidinib'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.

Speaker Change: In addition, we recently announced that this year, we plan to initiate a phase two clinical study in recurrent glioma and we look forward to providing more details about that study later this year.

We think this is an important opportunity as there is a significant unmet medical need in this patient population.

Speaker Change: We along with connect are excited about Alicia said and its potential to provide a much needed new treatment option to this I'm just.

Third patient population and we look forward to the data generation from the Kinect study. In addition to our planned study in recurrent liana.

Lisa Rojkjaer: On slide 26, you'll see another important collaboration, our strategic alliance with the MD Anderson Cancer Center to advance elutacidin more broadly into AML, MDS and beyond. We're pleased to report that the four studies indicated in this collaboration are now open for enrollment.

Speaker Change: On slide 26, you'll see another important collaborations our strategic alliance with MD Anderson cancer Center to advance a looser sit in the board broadly and two a M. L. M D S and beyond.

Speaker Change: We're pleased to report that the Florida studies indicated in this collaboration are now open for enrollment.

Speaker Change: Yeah.

Lisa Rojkjaer: Turning to our partner program. On slide 28, our RIPK1 inhibitor programs are progressing well with our partner, Lilly. RIPK1 is implicated in a broad range of inflammatory cellular processes and plays a key role in tumor necrosis factor signaling. Ocaducertib, our non-CNS penetrant RIPK1 inhibitor, previously referred to as R552, is currently being studied in an adaptive phase 2A, 2B clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis. Phase 2A enrollment of approximately 100 patients is advancing well with preliminary analysis of the results anticipated within the first half of 2025.

Speaker Change: Turning to our partnered program.

Speaker Change: On slide 28, our rent pay one inhibitor programs are progressing well with our partner Lilly.

Speaker Change: One is implicated in a broad range of inflammatory cellular processes in place the key role in tumor necrosis factor signaling.

Speaker Change: Oh could do searches are non CNS penetrant risk, Taiwan inhibitor previously referred to as our five five to six.

Speaker Change: Currently being studied in an adaptive phase two a two b clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis phase.

Stage, two way enrolment of approximately 100 patients is advancing well with preliminary analysis of the results anticipated within the first half of 2025.

Lisa Rojkjaer: Our preclinical CNS penetrant RIPK1 inhibitor program is also progressing toward lead candidate nomination.

Speaker Change: Our preclinical CNS penetrant grip K one inhibitor program is also progressing towards lead candidate nomination.

Lisa Rojkjaer: In closing, as you see on slide 29, there are several upcoming milestones for our development programs in 2025. For our R289 program and lower-risk MDS, we expect to complete the dose escalation portion of the Phase 1b study. The new 6-dose level, 500 mg twice daily, is actively enrolling. 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 the dose escalation data from the Phase 1b study in the second half of the year.

Speaker Change: In closing as you see on slide 29, there are several upcoming milestones for our development programs in 2025.

Speaker Change: For our art to wait nine program in lower risk Mds, we expect to complete the dose escalation portion of the phase <unk> study the new six dose level 500 milligrams twice daily is actively enrolling well.

Speaker Change: We then plan to initiate the dose expansion phase later this year.

Speaker Change: Also during the year, we plan to seek health authority and put on the Registrational path for our two late night.

Speaker Change: And we're anticipating presenting the dose escalation data from the phase <unk> study in the second half of the year.

Lisa Rojkjaer: Then for lutecidinibs, we plan to initiate a Phase II clinical study in recurrent glioma by year-end and also plan to provide you with more details about that study later this year. In addition, we'll continue to support the 4MD Anderson Studies and Connect Studies. We're excited about the progress we've made in 2024 to advance these programs and look forward to providing further updates on these planned milestones in 2025.

Speaker Change: And then for Luca sitting that we plan to initiate a phase II clinical study and were currently all met by year end and also plan to provide you with more details about that study later this year.

Speaker Change: In addition, we will continue to support the four M D. Anderson studies and connect study.

Speaker Change: We're excited about the progress we've made in 2020 forward to advance these programs and look forward to providing further updates on these planned milestones in 2025.

Dean Schorno: Now I'll pass the call to Dean to discuss our financial results for the quarter. Thank you, Lisa. I'm on slide number 31. We reported net product sales of $46.5 million for the fourth quarter, a growth of 58% year over year, including Tavolese, net product sales of $31 million, a growth of 21% year over year, Resolidium net product sales of $7.4 million, growth of 92% year over year, and Gabretto net product sales of $8.1 million in the fourth quarter. As a reminder, Gabretto became available from Rigel in June of 2024. Our net product sales from Tavolese, Resolidium, and Gabretto were recorded net of estimated discounts, chargebacks, rebates, returns, copay assistance, and other allowances of $19.7 million.

Dan: Now I'll pass the call to Dan to discuss our financial results for the quarter.

Dan: Thank you Lisa I'm on slide number 31, we reported net product sales of $46 $5 million for the fourth quarter, a growth of 58% year over year, including probably net product sales of $31 million or growth of 21% year over year, whereas median net product sales of $7 4 million.

Dan: Gross or 92% year over year, and Jeb Ryder net product sales of $8 $1 million in the fourth quarter. As a reminder, Jeb Ryder became available Rigel in June of 2024.

Dan: Net product sales from probably really in depth <unk> were recorded net of estimated discounts charge backs rebates returns co pay assistance and other allowances of $19 $7 million for the fourth quarter of 2024, our gross to net adjustment for Tomboyish, graduating caporetto was approximate 33.

Dean Schorno: For the fourth quarter of 2024, our gross to net adjustment for Tavolese, Resolidium, and Gabretto was approximately 33%, 21%, and 23% of gross product sales, respectively. Our fourth quarter revenues reflect strong patient demand and were aided by a year-end increase in inventory in our distribution channels that we've seen in the past. As we've also seen in the past, we expect to experience a drawdown in these inventory levels in our distribution channels in the first quarter of 2025. Incrementally, we highlighted in the fourth quarter we made certain changes to our distribution channel arrangements for tabloids that would result in continued high-quality access while reducing our distribution costs and favorably impacting our gross-to-net adjustment into the future.

Dan: 3%, 21% and 23% of gross product sales respectively.

Dan: Our fourth quarter revenues reflect strong patient demand and were aided by year end increase in inventory in our distribution channels and we've seen in the past.

Dan: Also seen in the past we expect to experience.

Dan: Drawdown of inventory levels in our distribution channels in the first quarter of 2025.

Dan: Incrementally we highlighted in the fourth quarter, we made certain changes to our distribution channel arrangements the top.

Dan: It would result in continued high quality access, while reducing our distribution costs and favorably impact our gross to net adjustments into the future.

Dean Schorno: While this change is not expected to impact our bottle ship to patients at clinics, we expect to experience a reduction in bottles remaining in our distribution channel of approximately 350 bottles during the first quarter of 2025. We expect the effect of these distribution channels will have normalized by the end of Q1. We also reported $11.1 million in contract revenues from our collaboration. for the fourth quarter, primarily driven by Griffith and Keysay, along with $4 million in revenue from Dr. Reddy's related to the upfront fee from sublicensing elutacitinib.

Dan: This change is not expected to impact our bottles shipped to patients critics, we expect to experience a reduction in bottles remaining in our distribution channel from approximately 350 bottles during the first quarter of 2025.

Dan: We expect the effect of these distribution channels will normalize by the end of Q1.

Dan: We also reported a $11 $1 million in contract revenue smart collaborations.

Dan: For the fourth quarter, primarily driven by reforming quayside, along with $4 million in revenue from Doctor revenues related to upfront fee from sub licensing or were just sitting there.

Dean Schorno: On to the next slide and moving down the income statement to cost and expenses. Our cost of product sales was approximately $5.8 million for the fourth quarter of 2024. Total cost and expenses were $40.9 million compared to $33.8 million for the same period of 2023. The increase in cost and expenses was mainly due to higher R&D costs driven by the timing of our clinical activities, increased personnel related costs, and increased commercial related activities. In addition, cost of product sales increased driven primarily by increased product sales, higher royalties, higher amortization of intangible assets, and sub-licensing revenue.

Dan: Yeah.

Dan: Onto the next slide and moving down the income statement to cost and expenses our cost of product sales was approximately $5 $8 million for the fourth quarter of 2024.

Dan: Total costs and expenses were $49 million compared to $33 $8 million for the same period of 2023.

Dan: The increase in cost and expenses was mainly due to higher R&D costs, driven by the timing of our clinical activities increased personnel related costs and increased commercial related activities. In addition cost of product sales increased driven primarily by increased product sales and higher royalties higher amortization.

Dan: Of intangible assets and sub licensing revenue.

Dean Schorno: For the full year, cost of product sales were approximately $18.6 million. Total cost and expenses were $155.1 million, compared to $137.4 million for the full year of 2022. The increase in cost and expenses was mainly due to higher cost of product sales, driven primarily by increased product sales, higher royalties, higher amortization of intangible assets, and sub-licensing revenue. In addition, there were increases in personnel related costs, stock based compensation expense, and commercial related expenses. These increases were partially offset by decreased R&D costs due to the timing of clinical trial activities related to R289, our dual IRAC1-4 inhibitor program, as well as reduced trial activities related to completed Phase III clinical trials during 2020.

Dan: For the full year cost of product sales were approximately $18 $6 million.

Dan: Total costs and expenses were 155 $1 million compared to $137 $4 million for Europe 2023.

Dan: Kris and cost and expenses was mainly due to higher cost of product sales driven primarily by increased product sales and higher royalties higher amortization of intangible assets and sub licensing revenue fees.

Dan: In addition, there were increases in personnel related costs stock based compensation expense and commercial related expenses.

Dan: Increases were partially offset by decreased R&D costs due to the timing of clinical trial activities related to our 289 or dual Iraq, one four inhibitor program as well as reduce trial activities related to completed phase III clinical trials turn into 2023.

Dean Schorno: We reported net income of $14.3 million for the fourth quarter, compared to $700,000 in the same period in 2023. For the full year, we reported net income of $17.5 million, compared to a net loss of $25.1 million for 2023. We ended the quarter with cash, cash equivalents, and short-term investments of $77.3 million, up from $56.9 million as of the end of 2023.

Dan: We reported net income of $14 $3 million for the fourth quarter compared to $700000 in the same period in 2023 for the full year, we reported net income of $17 $5 million compared to a net loss of $25 $1 million for 2023.

Dan: We ended the quarter with cash cash equivalents and short term investments of $77 $3 million up from $56 $9 million as at the end of 2023.

Dean Schorno: Turning to our financial outlook for 2025, we expect total revenue in the range of approximately $200 to $210 million, comprised of approximately $185 to $192 million in net product sales and $15 to $18 million of contract revenues from collaboration.

Dan: Turning to our financial outlook for 2025, we expect total revenue in the range of approximately $200 million to $210 million comprised of approximately $185 million to $192 million in that product sales.

Dan: $15 million to $18 million of contract revenues from collaborations.

Dean Schorno: We also anticipate reporting positive net income for the full year, while funding existing and new clinical development programs. To wrap up my section, 2024 was a tremendous year of revenue growth and continued financial discipline for Rigel, and we look to continue into 2025 and beyond.

Dan: We also anticipate reporting positive net income for the full year, while funding existing a new critical development programs.

Dan: Bye Bye. This action 2024 was a tremendous year of revenue growth and continued financial discipline for Rigel, and we look to continue into 2025 and beyond we thought I'd like to turn the call back over to Ralph.

Raul Rodriguez: With that, I'd like to turn the call back over to Raul. Thank you, Dean. Moving on to slide 33, as I've stated on this call, 2024 was a year of significant achievements for Rigel. We reach profitability and cash flow break even while delivering on our corporate strategy to grow our hematology and oncology business. Going forward into 2025, our priorities are clear, continue to grow our commercial business, advance our development programs, identify new pipeline opportunities, and continue to maintain financial discipline. We anticipate growing our net product sales by approximately 30% year over year. We remain focused on advancing our Phase 1B study of R289 for the treatment of lower risk MDS and complete the dose escalation portion of this study.

Dan: Moving on to Slide 33, as Ive stated on this call 'twenty 'twenty four whether Europe significant achievements for Roger.

Dan: We reached profitability and cash flow breakeven, while delivering on our corporate strategy to grow our hematology and oncology business.

Dan: Going forward into 2025, our priorities are clear continue to grow our commercial business.

Dan: That's our development programs and identify new pipeline opportunities and continue to maintain financial discipline.

Dan: We anticipate growing our net product sales by approximately 30% year over year.

Dan: We remain focused on advancing our phase <unk> study of arc <unk> nine for the treatment of lower risk Mds and complete the dose escalation portion of this study.

Raul Rodriguez: We plan to initiate the dose expansion phase of the study and provide the updated data at a medical meeting later this year. We plan to initiate a new Rigel-sponsored Phase II study in recurring glioma and continue to support our strategic collaborations with both MD Anderson and the CONNECT organization. Even with all these investments to advance our current and new pipeline programs, we expect to report positive net income for the full year of 2025.

Dan: To initiate the dose expansion phase of the study and provide the updated data at a medical meeting later this year.

Dan: Or lose it and that we plan to initiate a new rigel sponsored phase II study in recurrent glioma and continue to support our strategic collaborations with both M. D. Anderson interconnect organization.

Dan: Even with all these investments to advance our current and new pipeline programs. We expect to report positive net income for the full year of 2025.

Raul Rodriguez: Moving on to slide 34. I'm thrilled that Rigel has reached this pivotal point in the company's history. Our implementation of our corporate strategy has brought us to a place where our commercial sales levels now allow us to grow the business in a profitable and sustainable manner. It's a really exciting time for the company.

Dan: Let me go on to Slide 34, I am thrilled that rightful has reached this pivotal point in the company's history. Our implementation of our corporate strategy has brought us to a place where our commercial sales levels now allow us to grow the business in a profitable and sustainable manner.

Dan: Really exciting time for the company and with that I'd like to turn the call over to your questions.

Unknown Executive: And with that, I'd like to turn the call over to your questions. Thank you. At this time, we'll begin our question and answer session.

Dan: Thank you.

Dan: At this time, we will begin a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad.

Unknown Executive: If you would like to ask a question, please press star one on your telephone keypad. To remove yourself from the queue, please press star 2. Again, to ask a question, press star one on your telephone.

Dan: To remove yourself from the queue. Please press star two.

Dan: Once again to ask a question press star one on your telephone keypad.

Yigal Nochomovitz: And our first question comes from Yigal Nochomovitz with Citi.

Dan: And our first question comes from you got them the trouble of it with Citi. Please state your question.

Dean Schorno: Please state your question. Hi guys, thanks so much for taking the questions. I have a few. The first one on the product guidance, I think you said $192 to $195. So using the fourth quarter as a base, could you just give a little more color as far as the comments there in terms of the range? It seems a little conservative. It looks like it's about a 1 to 2% quarter-on-quarter CAGR going off the 4Q base. That was my first question.

Speaker Change: Hi, guys. Thanks, so much for taking the questions I have a few the first one on the.

Speaker Change: <unk> guidance I think you said 192 to 195, so using using the fourth quarter as a base I'm just could you just give a little more color as far as the.

Speaker Change: The the comments there in terms of the range it seems a little conservative it.

Speaker Change: It looks like it's about a 1% to 2% quarter on quarter CAGR.

Speaker Change: I'm going off the <unk> base that was my first question. Thank you.

Yigal Nochomovitz: Thank you. Yes, so the net revenue guidance is for 185 to 192. And the Q4 was $46.5 million of net product sales. That was aided by, as we said in our prepared comments, it was aided by inventory billed in Q4. And we've seen this typically, that accounted for about $4.5 million of that $46.5 million of net revenues in Q4. So as you normalize that, and you start to build Q1 through Q4, that creates the revenue guidance that we described. And that represents at the midpoint about a 30% year-over-year growth in net product sales.

Speaker Change: Yeah. So the so the net revenue guidance is for 185 to 192.

Speaker Change: And the Q4.

Speaker Change: <unk> was $46 $5 million of net product sales that was aided by.

Speaker Change: And as we said in our prepared comments it was aided by an inventory build in Q4 and we've seen this typically that accounted for about $4.5 million of about $46 $5 million of.

Speaker Change: Net revenues in Q4, so if you normalize that and you start to build our Q1 through Q4 that creates the revenue guidance that we described and that represents at the midpoint about 30% year over year.

Gross and net product sales.

Yigal Nochomovitz: Okay, thanks, Dean.

Speaker Change: Okay. Thanks, Dean and then I'm curious on and whereas linear do you have any data from the field in terms of the duration of therapy. There I recall from a couple of years ago. There was some very very good data you had showing the <unk>.

Yigal Nochomovitz: And then I'm curious on Reslydia, do you have any data from the field in terms of the duration of therapy there? I recall from a couple of years ago, there was some very, very good data you had showing the strength of that durability.

Speaker Change: The strength of that that durability.

David Santos: Yigal, great question.

Speaker Change: Yeah. Great question. This is Dave we won't share any of that today, but what I can tell you is we have a lot of room to grow them at the end of the day you know whenever you launch a product and we're only two years into this year.

David Santos: This is Dave. We won't share any of that today. But what I can tell you is we have a lot of room to grow. At the end of the day, you know, whenever you launch a product, and we're only two years into this, you're going to get a lot of later line patients and those patients, you know, are not going to have the duration of therapy that you would have seen in the clinical trial where they were probably in the second line, or third line setting. And so, you know, that's kind of where we are right now.

Speaker Change: Get a lot of later line patients and those patients you know are not going to have the duration of therapy that you would.

Speaker Change: It would have seen in the clinical trial, where they were probably in the second line or.

Speaker Change: For third line setting and so you know that's kind of where we are right now. So obviously, we do believe our duration of therapy is a significant driver of them you know.

David Santos: So obviously, we do believe our duration of therapy is a significant driver of, you know, adoption, but also a significant driver of carryover as we move forward. That's why I'm optimistic about our ability to grow as awareness grows, as we get more patients on therapy, and we get earlier patients on therapy, particularly those who've had first line venetoclax. We think we can drive duration higher.

Speaker Change: Adoption, but also a significant driver of carryover is would be for it that's why I'm optimistic about our ability to grow as awareness grows as we get more patients on therapy, and we get earlier patients on therapy, particularly those who had first line, but at a class a we think we can drive duration higher.

Speaker Change: Yeah.

Yigal Nochomovitz: Thanks.

Yigal Nochomovitz: And just one last one, if I might.

Speaker Change: Thanks, and just one last one if I might.

David Santos: Do you have any data as to the percent of patients that are on Govretto by Rigel versus Govretto from the prior commercial sponsor? I don't have specific data, but I can tell you, you know, our goal was to transition every single patient that was on Gavretto over to Rigel Label Products. I think the fact that we sold $8.1 million and that our demand grew from Q3 to Q4, and our run rate was higher than the previous run rate of $28 million last year, I think we achieved that. So I really don't think we lost any patients in the mix, and as a matter of fact, obviously, I think we're adding new patients.

Speaker Change: Do you have any data as to the percent of patients that are on give rado by rigel versus the red Oh from the prior commercial sponsor.

Speaker Change: I don't have specific data, but I can tell you you know our goal is to transition them every single patient that was on gift Reno over to Raj and label products.

Speaker Change: Thank the fact that we sold $8.1 million and that our demand grew from Q3 to Q4.

Speaker Change: And our run rate was higher than the previous run rate of $28 million last year. I think we achieved that I really don't think we lost any patients in the mix and as a matter of fact, obviously I think we're adding new patients. It's hard for us at this point in time to say new patients on brand versus new.

David Santos: It's hard for us at this point in time to say new patients on brand versus new patients to Rigel. We know they're all new patients to Rigel, but we think we are getting new patients to brand because our demand continues to move up.

Speaker Change: Patients to Rigel, we know, they're all new patients to rigel, but we think we are getting new patients to brand because our demand continues to be about.

David Santos: You know, that was a pretty remarkable achievement, that transition, because you typically see a sell of a product from one company to another, and for probably six months, you see a lower sales base than originally before, and that wasn't the case here. So this is really pretty remarkable that we achieved that, and we're really pleased with it. It also shows that we have the entirety of the team, medical affairs, market access, the sales organization, really focused on the right things and getting those patients across, and so it really worked remarkably well.

Speaker Change: That was a pretty remarkable achievement that transition because you typically see a sellable product from one company to another.

Speaker Change: Probably six months, you'll see a lower sales base than the originally before and that wasn't the case here. So this is really pretty remarkable that we achieve that and really pleased with but also shows that we have the entirety of the team about a medical affairs market access are the sales organization really focused on the right things and getting them.

Speaker Change: Those patients across and so we've really worked remarkably well I'm actually incredibly impressed.

Yigal Nochomovitz: I'm actually incredibly impressed. Got it.

Yigal Nochomovitz: Thank you very much for taking the question. Thank you.

Speaker Change: Got it. Thank you very much for taking my question.

Speaker Change: Thank you and our next question comes from cockpit Patel with B Riley Securities. Please state your question.

Kalpit Patel: And our next question comes from Kalpit Patel with B. Reilly Securities. Yeah, hey, good afternoon. And thanks for taking the question. Maybe I want to start first with with the Taveli sales, the increase in the fourth quarter relative to the third quarter. Maybe comment on how much of that was an organic volume increase versus maybe any pricing increases that may have occurred? I'm sorry, can you repeat the last part of your question, Kalpit? You said volume versus... Yeah, like, yeah, exactly. Just, you know, was this accounted for by any price? Yeah, we didn't have any price increase in Q4.

Cockpit Patel: Yeah, Hey, good afternoon, and thanks for taking the question.

Cockpit Patel: Maybe I wanted to start first with the Teva lease sales the increase in the fourth quarter relative to the third quarter.

Cockpit Patel: Maybe comment on how much of that was organic volume increase versus maybe any price increases that may have occurred.

Cockpit Patel: I'm sorry can you repeat the last part of your question you said volume versus.

Cockpit Patel: Yeah I like the.

Cockpit Patel: Yeah exactly.

Cockpit Patel: Was this accounted for by.

Cockpit Patel: Any price increases.

Cockpit Patel: Yeah, we didn't have any price increase in Q4. So that was all volume what I will say is we had our highest quarterly demand ever that order was shipped to patients and clinics as a matter of fact, it was the ninth consecutive quarterly high that we'd hit we also had a.

David Santos: So that was all volume. What I will say is we had, you know, our highest quarterly demand ever that's been auto shipped to patients and clinics. Matter of fact, it was the ninth consecutive quarterly high that we hit. We also had a higher percentage of new patients starts, or new patients versus existing patients kind of driving that volume in fourth quarter. And so again, as Dean said, we were also aided by some inventory bill, which is typical in the last in the last quarter. But demand definitely increased from Q3 to Q4 as a new patient starts.

Cockpit Patel: A higher percentage of new patient starts are.

Cockpit Patel: Our new patients versus existing patients kind of driving that volume in fourth quarter and so again as Dean said, we were also aided by some inventory build which is typical in the last in the last quarter of the year, but demand definitely increased from Q3 to Q4.

Speaker Change: As in new patient starts and we did we did a press release highlighted the uniform demand volume out as David suggested the demand or the the bottles shipped to patients at clinics, that's really the key to the business. That's the those are the bottles that are going to you know go to patients.

David Santos: And we did, we did our press release highlight the unit volume, the demand volume, as Dave suggested, the demand or the bottle ship to patients and clinics, that's really the key to the business. That's the, those are the bottles that are going to go to patients. Incrementally, there's the bottles left in the distribution channels that we report, and those are inventory levels. For Tabulis, that inventory level benefit for Q4 was about $3 million, and that's in the 4.5 million I described. Again, Tabulis was benefited by about $3 million. That said, again, the demand is consistently growing, and that's the important measure of the business.

Speaker Change: Italy, there's the the bottle is left in the distribution channels that we report.

Speaker Change: And those are inventory levels for top of we use that inventory level benefit for Q4 was about $3 million and that's in the $4 5 million I described.

Speaker Change: Probably used was benefited by about $3 million that said again the demand is consistently growing and that's the important measure of the business.

Kalpit Patel: Okay, okay, great.

Speaker Change: Okay, Okay, great and then maybe switching over to your.

Kalpit Patel: And then maybe switching over to your glioma program, the planned study. I know you're still working on the design there. But I'm curious on the strategy here.

Speaker Change: The planned study I know you're still working on the design there.

Speaker Change: But I'm curious on the strategy here are you going to do a head to head study against divorce at Nab or are you trying to maybe position your drug for a different grade agree on Bobby maybe a higher grade a grade three or four.

Raul Rodriguez: Are you going to do a head to head study against borosidnib? Or are you trying to maybe position your drug for a different grade glioma, maybe a higher grade, a grade three or four? Thanks for the question. I think at this point it's still too early to comment on the design of the study. We've just kind of started our KOL discussions and ad boards and are working on that plan, but we'd certainly be happy to give you more information on this later in the year. So for both 289 and Olura and Guayoma, our plan is to later this year, as we have some discussions with regulatory agencies and settle on what the plan is exactly, we'll come back to you and share that with you.

Yeah. Thanks for the question I think at this point, it's still too early to comment on the design of the study. We've just kind of started our kols discussions and AD boards that are working on that plan, but we'd certainly be happy to give you more information on this later in the year.

Speaker Change: So for both to ignore Linda alluded in Glioma. Our plan is to later this year as we have.

Speaker Change: Some discussions with regulatory agencies and settled on what the plan is exactly we'll come back to you and ensure that with you.

Raul Rodriguez: But it probably will be in the second half.

Speaker Change: We will be in the second half of the year.

Kalpit Patel: Okay, great.

Kalpit Patel: Thank you very much.

Speaker Change: Okay, great. Thank you very much.

Joe Pantginis: Thank you. And our next question comes from Joe Pantginis with HC Wainwright. Hi everybody. Good afternoon. Thanks for taking the questions. So my first question is a two-parter for Tavilis if you don't mind. So in the U.S.

Speaker Change: Thank you and our next question comes from Joe Pat Tennis with H C. Wainwright. Please state your question.

Speaker Change: Hi, everybody good afternoon, and thanks for taking the questions. So my first question is a two parter for tab at least if you don't mind. So in the U S. I guess, how would you describe.

Joe Pantginis: I guess how would you describe, well first can you describe the difference or the percentages of refills and the growing aspect of new prescriptions and what are you doing to help grow new prescriptions say today versus where you were you know one to two years ago. That's part one. Yes, I think, great question, Joe. I think, as I said before, what we noticed in Q4, which was really nice, is that a larger percent of our patients, and that's total patients on therapy, those who are carrying over from previous quarters, as well as new patients, a higher percentage was driven by new patients.

Speaker Change: Well first can you describe the difference or the percentages of refills in the growing aspect of new prescriptions and what are you doing to help grow new prescriptions say today versus where you were you know one to two years ago, that's part one.

Speaker Change: Yeah. So I think great question, Joe I think as I said before what we noticed in Q4, which was really nice is that a larger percentage of our patients and that's total patients on therapy, those who are carrying over from previous quarters as well as new patients are higher percentage was.

Speaker Change: Driven by new patients so as a matter of fact, the highest percentage we've ever seen and so clearly I think you know adoption is growing I think some of the things that we're doing now that we've learned over the past is certainly you know targeting of of clinicians who something we've spent a lot of time and effort.

David Santos: As a matter of fact, the highest percentage we've ever seen. And so, clearly, I think, you know, adoption's growing. I think some of the things that we're doing now that we've learned over the past is certainly, you know, targeting of clinicians is something we've spent a lot of time and effort to make sure that we're doing. Expanding reach through different channels is another thing that we're doing. And then, I think, the last part is, you know, community practices play a big role in the management of ITP. And I think, you know, we target the specific TPOs out there among the community practices to ensure that they're aware of ITP's unique value proposition.

Speaker Change: To make sure that we're doing are expanding reach through different channels is another thing that we're doing and then I think the last part is you know many practices play a lot a big role in the management of I T. P and I think you know we target the specific.

Speaker Change: A T P o's out there among the community practices.

Speaker Change: To ensure that they're aware of our of Itt's unique value proposition.

David Santos: or unique value proposition in ITP, sorry.

Speaker Change: So that unique value proposition 90 P. Sorry, no of course, so and part two is I guess, taking some of the components that you were just discussing I wanted to discuss the ex U S opportunities as you expand geographically are there any components that are unique to ex U S.

David Santos: No, of course, so and part two is, I guess, taking some of the components that you were just discussing, I want to discuss the XUS opportunities as you expand geographically. Are there any components that are unique to XUS? Like you said, community centers, for example, how are they, you know, how is the drug delivered there? Are there differences in the initial lines of therapy? Any particular components you can point to XUS that might differ from the U.S.? I think the best thing for me to do is kind of talk about how the U.S. may be unique in that its use of T-pose and particularly end plate is probably more driven by that community practice kind of buy and build sort of mentality.

Speaker Change: Like you said community centers for example, how are they you know how is the drug delivered there or are there differences in the initial lines of therapy and any particular.

Speaker Change: Components, you can point to ex U S that might differ from the U S.

Speaker Change: Yeah, I think the best way for me to do is kind of talk about how the U S may be unique in that its use of our people and it is particularly and play them is is probably more driven by you know that community practice kind of buy and bill.

Speaker Change: Sort of mentality.

David Santos: And I think, you know, particularly in Japan, some of the differences there that they've seen is, you know, a higher willingness to use combination therapy. And so I think there are some differences across the globe in how patients are treated and the way clinicians approach ITP management. But like I said, here in the U.S. it's a lot, it's treated, you know, it's not a disease, it's a benign hematologic condition where if a hematologist, oncologist sees this, you know, they're not going to refer it, they're going to treat it. So I think, you know, we have a very kind of diffuse model here in the U.S.

Speaker Change: And I think our you know, particularly in Japan, and some of the differences there that they've seen is a you know.

Speaker Change: A more a higher willingness to use combination therapy.

Speaker Change: And so I think there are some differences across the globe in how patients are treated and and the way.

Speaker Change: Clinicians approach I T T management, but like I said here in the U S. It's a lot it's treated.

Speaker Change: Not it's not a disease, it's a benign hematologic condition, where if a hematologist oncologist thesis are you know, they're not going to refer it they're going to treat it.

Speaker Change: So I think you know we have a very kind of diffuse model here in the U S, which I think it might be a little more concentrated than in other countries outside the U S.

Joe Pantginis: which I think might be a little more concentrated in other countries outside the U.S. No, that's helpful. I appreciate that color.

Speaker Change: No. That's helpful. I appreciate that color and then my last question. If you don't mind, it's more of an infrastructure question. So as of right. Now would you define your sales force at as right sized and as you look to add assets in or an early launch stages. You know what would you envision as potential <unk>.

David Santos: And then my last question, if you don't mind, is more of an infrastructure question. So, as of right now, would you define your sales force as right sized? And as you look to add assets and are in early launch stages, you know, what would you envision as potential growth of the size of your sales force?

Speaker Change: Growth of the size of your sales force. Thanks.

David Santos: Thanks. Yeah, great question, Joe. I would say that, you know, what we've done with ResLydia and GetReto is ensure that we have synergies. And it's not just sales, right? It's across the brand team. It's across market access, which is a big component in commercializing products these days, as well as our operational and analytical capabilities in business operations. So we have tremendous synergies there. But, you know, I'll just say that we're constantly looking at our impactable market and how many customers we need to call on to ensure that we create impact, positive impact on our brands in the market.

Speaker Change: Yeah, Great question, Joe I would say that you know what we've done with red linear and get right I always ensure that we have synergies and it's not just sales Ryan it's across the brand team it's across market access which is a big component.

Speaker Change: In commercializing products these days as well as our operational and analytical capabilities and business operations. So we have tremendous synergies there, but you know I'll just say that our art. We're constantly looking at are impactful market and who how many customers we need to call on to it.

Speaker Change: Sure that we create impact positive impact on our brands in the market and depending on the product we bring aboard the sub specialists that might be involved.

David Santos: And depending on the product we bring aboard, the subspecialists that might be involved, it could vary in terms of whether we would need to build sales support or not. And if it's something that is used primarily in the community, then I think we have the capacity to cover. But if it's something that's in a subspecialty that we're maybe not calling on today, then obviously we need to address it. But how did the assessment of the each of those individual opportunities as we decide to bring them in or Sure, sure.

Speaker Change: It can vary in terms of whether we would need to build sales.

Speaker Change: Our sales support or not and if it's something that is used primarily in the community or then I think we have the capacity to cover but if it's something that's been a sub specialty that might that were maybe not calling on today, then obviously, we'd need to address that.

Speaker Change: But it'll be assessment of each of those individual opportunities as we decided to bring them in or not.

Joe Pantginis: Thank you for all the comments. Thank you, Joe.

Speaker Change: Sure sure. Thank you for all the comments.

Joe Ryan: Thank you Joe.

Speaker Change: Yeah.

Speaker Change: Okay.

Kristen Kluska: Your next question comes from Kristen Kluska with Kantor. Please state your question. Hi, this is Ayaan on Kristen's line. Thank you for taking our questions. Could you talk a bit about your plan to initiate the expansion phase of the first one of the phase one study of R289 this year? Any color you can provide here, particularly when you plan to start and how you go about choosing the doses?

Speaker Change: Your next question comes from Kristen <unk> with Cantor. Please state your question.

Speaker Change: Hi, This is Ian Unquestioned line. Thank you for taking our question could you talk a bit about your plan to initiate the expansion phase of that first one.

Speaker Change: There's one study of our 289 this year any color you can provide here, particularly when you plan to start and how you thought about using the telephones.

Lisa Rojkjaer: Yeah, thanks for the question. Um, as you know, as I mentioned, we're currently enrolling in dose level six for dose escalation. So first thing we're going to have to do is complete enrollment at that dose level and have a look at the, the safety and activity. Um, dose selection for expansion, um, will be based on, you know, the typical things like safety, PK, PD, uh, you know, a little bit of activity. Um, as you see on the, you may have noticed on the slide, we, we plan to enroll up to 20 patients per arm, because we really want to conduct a robust determination of, uh, of a dose to carry forward and to, for further clinical evaluation.

Speaker Change: Yeah. Thanks for the question as you know as I mentioned, we're currently enrolling in dose level six for dose escalation.

Speaker Change: So first thing we're going to have to do is complete enrollment at that dose level and have a look at the the safety and activity.

Speaker Change: Dose selection for expansion.

Speaker Change: Well be based on.

Speaker Change: So typical things like safety PK P D a little bit of activity.

Speaker Change: As you see on the you may have noticed on the slide we plan to enroll up to 20 patients per arm, because we really want to conduct a robust determination.

Speaker Change: Oh, the dose to carry forward into further clinical evaluation and so as we mentioned we're looking forward to opening that later this year and the exact timing of that as I mentioned will really depend on.

Lisa Rojkjaer: Um, so as we mentioned, we're looking forward to, um, opening that later this year. And the exact timing of that, um, as I mentioned, will really depend on, um, what's going on in dose escalation in this last cohort. That's helpful. Thank you so much. Thank you.

Speaker Change: What's going on in dose escalation in this last cohort.

Speaker Change: Okay.

Speaker Change: That's helpful. Thank you so much.

Speaker Change: Thank you and remind ourselves.

Unknown Executive: And a reminder to the audience, to ask a question now, press star 1 on your telephone keypad. To remove yourself from the queue, press star 2. Once again, to ask a question, press star 1 on your telephone keypad.

Speaker Change: And a reminder to the audience to ask a question now press star one on your telephone keypad to remove yourself from the queue Press star two once again to ask a question press star one on your telephone keypad.

Farzin Haque: Our next question comes from Farzin Haque with Jefferies Police. Hi, thank you for taking my question. Also on R289 low risk MDS program. So I wanted to ask on the further dose evaluations that are ongoing with split dosing, how are you setting expectations there? And then timing for the data updates, will it be more of an Azure update in the second half? Yeah, so, as you noticed in our, and thanks for the question, very interesting, as you noticed, during the course of the dose escalation phase, we changed TAC from once daily to twice daily dosing, because we think, biologically, it makes more sense to have a more or less continuous suppression of inflammation as opposed to kind of an on-off, on-off.

Speaker Change: Our next question comes from Farseeing HOKA with Jefferies. Please state your question.

Speaker Change: Hi, Thank you for taking my question also on <unk> 289, low risk Mds program. So wanted to ask on the fact that those evaluations that are ongoing with the split dosing how he's sitting expectations. There and then timing for the data updates will it be more of an ash update in second half and then have a follow up.

Speaker Change: Yeah. So as you noticed in our auto and thanks for the question very interesting as you noticed him during the course of the the dose escalation phase we changed tack from once daily to twice daily dosing, because we think biologically it makes more.

Speaker Change: Our sense to have a.

Speaker Change: More or less continuous suppression of inflammation as opposed to kind of an on off on off.

Lisa Rojkjaer: So, we're really looking forward to seeing the data from the BID dose levels, and related to the anticipated timing of the data presentation, well, I think our best opportunity is ASH, so we're anticipating having an opportunity there to present the updated study data. Keep in mind that we want to have four to six months of exposure in each of these patients in order to properly assess whether the product's working, its efficacy, and importantly, its safety. So that does take some time to do that. So it by necessity has to be towards the end of the season.

Speaker Change: So we're really looking forward to seeing the data from the B I D.

Speaker Change: Dose levels.

Speaker Change: And related to the.

Speaker Change: Anticipated timing of the data presentation, well I think our best opportunity is ash, so where we're anticipating having an opportunity there to present the updated study data.

Speaker Change: For them to keep in mind that we want to have four to six months of exposure in each of these patients in order to properly assess where the product's working its efficacy. Its importantly safety. So that does take some time to do that so by necessity has to be towards the end of this calendar year.

Farzin Haque: Got it. That makes sense.

Speaker Change: Got it that makes sense and then I will be waiting for the match your dose escalation data prior to the meeting with the regulators to play a registrational path.

Lisa Rojkjaer: And then I will be waiting for the mature dose escalation data prior to meeting with the regulators for a registrational patch. I think we'll give some more information on that later as the data mature more. So we won't wait till the end of the year to have some interaction with them. The nice thing about fast track designation is that it allows them and us to work more closely together. That's really helpful. Thank you so much. Thank you.

Speaker Change: I think we will give some more information on that later as the data mature.

But we won't wait till the end of the year to have.

Speaker Change: Some interaction with them the nice thing about fast track designation is that it allows them and us to work more closely together that's really helpful.

Speaker Change: Got it thank you so much.

Speaker Change: Thank you.

Unknown Executive: And there are no further questions at this time.

Speaker Change: There are no further questions at this time I would like to turn the floor back over to Mr. Raul Rodriguez for closing comments well. Thank you I'd like to thank you for joining this call today and your good questions Oh, and specifically for your continued interest in Rigel, it's been Oh really monumental year for US we're really proud of what we achieved in 2024.

Raul Rodriguez: I would like to turn the floor back over to Mr. Raul Rodriguez for closing comments. Well, thank you. I'd like to thank you for joining this call today and your good questions, and specifically for your continued interest in Rigel. It's been a really monumental year for us. We're really proud of what we achieved in 2024 and incredibly excited about 2025. We have some significant things ahead of us, and I think we're really well positioned to execute successfully against them.

Speaker Change: And incredibly excited about 2025, we have some significant things ahead of us and I think we're really well positioned to execute successfully against them before we leave I'd like to thank our employees for their continued interest in improving the lives of patients and for making 2020 for such a successful year for us so with that look forward to.

Raul Rodriguez: Before we leave, I'd like to thank our employees for their continued interest in improving the lives of patients and for making 2024 such a successful year for us. So, with that, look forward to updating you on future calls and have a great day.

Speaker Change: Updating you on future calls and have a great day.

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

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