Rigel Pharmaceuticals, Inc. (RIGL) 2025 Q4 法說會逐字稿

Greetings, and welcome to the Rigel Pharmaceuticals financial conference call for the fourth quarter and full year 2025. (Operator Instructions) As a reminder, this conference is being recorded.

各位好，歡迎參加 Rigel Pharmaceuticals 2025 年第四季及全年財務電話會議。（操作說明）提醒各位，本次會議正在錄音。

It is now my pleasure to introduce our first speaker, Ray Furey, Rigel's Executive Vice President, General Counsel and Corporate Secretary. Thank you, Mr. Furey, you may begin.

現在，我很榮幸地向大家介紹我們的第一位演講嘉賓，Rigel 的執行副總裁、總法律顧問兼公司秘書 Ray Furey。謝謝您，弗雷先生，您可以開始了。

Welcome to our fourth quarter and full year 2025 financial results and business update conference call. The financial press release for the fourth quarter and the full year 2025 for the -- and full year 2025 was issued a short while ago and can be viewed along with the slides for this presentation in the News and Events section of our Investor Relations site on rigel.com.

歡迎參加我們2025年第四季及全年財務業績及業務更新電話會議。本公司已於不久前發布了 2025 年第四季及全年財務新聞稿，您可以在 rigel.com 投資者關係網站的「新聞與活動」部分查看該新聞稿以及本次簡報的幻燈片。

As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 2025, on file with the SEC.

再次提醒大家，在今天的電話會議中，我們可能會就我們的財務前景以及監管和產品開發的計劃和時間表發表前瞻性聲明。這些聲明存在風險和不確定性，可能導致實際結果與預測結果不同。有關這些風險的描述，請參閱我們向美國證券交易委員會提交的截至 2025 年 12 月 31 日的最新年度報告（表格 10-K）。

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

所有前瞻性陳述僅代表截至今日的觀點，我們不承擔任何義務更新這些前瞻性陳述以反映後續事件或情況。

At this time, I'd like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez. Raul?

此時，我想把電話交給我們的總裁兼執行長勞爾·羅德里格斯。勞爾？

Thank you, Ray, and thank you all for joining us today. Also with me are Dave Santos, our Chief Commercial Officer; Lisa Rojkjaer, our Chief Medical Officer; and Dean Schorno, our Chief Financial Officer. On today's call, I will provide an overview of Rigel's business, our accomplishments for the fourth quarter and full year 2025 as well as our strategic initiatives to drive growth.

謝謝你，雷，也謝謝今天所有到場的各位。與我同行的還有我們的商務長戴夫·桑托斯；我們的首席醫療官麗莎·羅伊克亞爾；以及我們的財務長迪恩·肖諾。在今天的電話會議上，我將概述 Rigel 的業務、我們在 2025 年第四季和全年的成就，以及我們推動成長的策略舉措。

Beginning on slide 4. I will outline Rigel's transformational growth strategy in hematology and oncology. For those of you less familiar with Rigel, our strategy is built around four core strategic objectives: grow our commercial business, expanding our portfolio through in-licensing or acquisition, advancing our clinical development pipeline and maintaining financial discipline. These four pillars are interlocking and collectively drive Rigel's long-term growth. Today, I will highlight how we've executed on this strategy since 2020, building Rigel into the profitable company we are today and how this framework positions us for continued growth in the years ahead.

從第4張投影片開始。我將概述Rigel在血液學和腫瘤學領域的轉型成長策略。對於不太了解 Rigel 的人來說，我們的策略圍繞著四個核心策略目標：發展我們的商業業務，透過引進許可或收購擴大我們的產品組合，推進我們的臨床開發管線，以及保持財務紀律。這四大支柱相互關聯，共同推動Rigel的長期發展。今天，我將重點介紹自 2020 年以來我們如何執行這項策略，將 Rigel 打造成如今這樣一家盈利的公司，以及這一框架如何使我們在未來幾年繼續保持成長。

Moving on to slide 5. Let me begin by outlining the transformation at Rigel over the last five years. In 2020, Rigel was a single product company. TAVALISSE was our only approved product indicated for the treatment of adult chronic ITP. Our development pipeline was limited, and the company was operating with negative cash flows. Now at the end of 2025 and now entering into 2026, we are fundamentally a different company. We now have three commercial products, TAVALISSE, REZLIDHIA and GAVRETO, approved for four different indications.

接下來是第5張投影片。首先，讓我概述一下Rigel在過去五年中的變化。2020年，Rigel還是一家單一產品公司。TAVALISSE 是我們唯一核准用於治療成人慢性 ITP 的產品。我們的研發項目有限，公司一直處於負現金流狀態。現在到了 2025 年底，進入 2026 年，我們已經從根本上變成了一家不同的公司。我們現在有三款商業產品，分別是 TAVALISSE、REZLIDHIA 和 GAVRETO，已獲準用於四種不同的適應症。

Our development pipeline is led by R289, a dual IRAK1/4 inhibitor discovered at Rigel. R289 is currently being evaluated in patients with lower-risk MDS, a potentially large commercial opportunity with significant unmet need. R289 offers a novel mechanism, attenuating the hyperinflammatory signal present in lower-risk MDS and so may offer a new approach to lower-risk MDS and potentially other diseases. Later in this presentation, Lisa will speak to the encouraging results from our Phase 1b study that were presented at the ASH meeting in December. And our financial position is fundamentally different today.

我們的研發管線以R289為首，R289是Rigel公司發現的一種雙重IRAK1/4抑制劑。R289 目前正在對低風險 MDS 患者進行評估，這是一個潛在的巨大商業機會，存在著巨大的未滿足需求。R289 提供了一種新的機制，可以減弱低危險群 MDS 中存在的過度發炎訊號，因此可能為低危險群 MDS 以及其他疾病提供一種新的治療方法。在本次演講的後半部分，Lisa 將談到我們在 12 月的 ASH 會議上公佈的 1b 期研究的令人鼓舞的結果。如今，我們的財務狀況已截然不同。

Rigel is profitable and has been since the third quarter of 2024. Since then, we have increased our cash position by more than $100 billion. This progress reflects disciplined capital allocation, thoughtful portfolio expansion and consistent execution across operations. Now looking ahead to 2030, we plan again to be a fundamentally different company. We are building on the commercial momentum of our three commercial products while selectively pursuing late-stage in-licensing and acquisition opportunities to further expand our commercial portfolio.

Rigel 自 2024 年第三季以來一直獲利。自那時以來，我們的現金儲備增加了超過1000億美元。這項進展反映了嚴格的資本配置、深思熟慮的投資組合擴張以及營運中始終如一的執行力。展望2030年，我們計畫再次成為一家截然不同的公司。我們正在鞏固三款商業產品的商業發展勢頭，同時有選擇地尋求後期引進許可和收購機會，以進一步擴大我們的商業產品組合。

At the same time, we will continue to advance R289 in lower-risk MDS and potentially additional indications. These indications will be areas of significant unmet need, and so our large commercial opportunities that again would be transformational for Rigel. As illustrated on slide 6, Rigel has delivered strong net product sales growth since emerging from the COVID pandemic. Based on the midpoint of our 2026 net product sales guidance of $260 million, we are achieving a compound annual growth rate of approximately 35% since 2022. This performance reflects strong commercial execution and successful portfolio expansion.

同時，我們將繼續推進 R289 在低風險 MDS 及其他潛在適應症的應用。這些跡象表明，存在著巨大的未滿足需求，因此也蘊藏著巨大的商業機遇，這將再次對 Rigel 產生變革性的影響。如幻燈片 6 所示，自 COVID-19 疫情爆發以來，Rigel 的淨產品銷售額實現了強勁成長。根據我們 2026 年淨產品銷售額指引值的中點 2.6 億美元計算，自 2022 年以來，我們的複合年增長率約為 35%。這一業績反映了強大的商業執行力和成功的產品組合擴張。

What is even more compelling is the opportunity ahead, driven by the growth of our current products, additional in-licensed or acquired products and particularly R289 in lower-risk MDS and other indications. These programs represent potentially billion-dollar opportunities that will expand our commercial portfolio in the 2030s and beyond. This strategy creates a clear road map for sustained growth and long-term shareholder value creation. Before I turn the call over to the rest of the team to discuss our other strategic objectives, I want to briefly highlight our approach to in-licensing and business development.

更具吸引力的是未來的機遇，這得益於我們現有產品的成長、其他引進或收購的產品，特別是 R289 在低風險 MDS 和其他適應症方面的應用。這些項目代表著潛在的數十億美元機遇，將在 2030 年代及以後擴大我們的商業組合。該策略為持續成長和長期股東價值創造制定了清晰的路線圖。在將電話交給團隊其他成員討論我們的其他策略目標之前，我想先簡單介紹一下我們在引進許可和業務發展方面的方法。

Moving to slide 8. We have a proven track record in business development, demonstrated by our acquisitions of REZLIDHIA and GAVRETO. Leveraging our existing commercial infrastructure, we efficiently incorporated both products into our portfolio with limited integration costs and operating expenses. As a result, a significant portion of those products revenue have contributed to our profitability and cash generation. As we evaluate future opportunities, we are focused on differentiated assets in hematology, oncology or closely related areas. We are seeking late-stage assets that have completed registrational trial, are NDA ready or under review or are already commercially available.

切換到第8張投影片。我們在業務發展方面擁有良好的業績記錄，我們收購了 REZLIDHIA 和 GAVRETO，就證明了這一點。利用我們現有的商業基礎設施，我們以有限的整合成本和營運費用，有效地將這兩款產品整合到我們的產品組合中。因此，這些產品收入的很大一部分都為我們的獲利能力和現金流做出了貢獻。在評估未來機會時，我們專注於血液學、腫瘤學或密切相關領域的差異化資產。我們正在尋找已完成註冊試驗、已準備好提交新藥申請或正在接受審查或已上市的後期資產。

These late-stage assets are targeted opportunities that would be launched within the next three years, ideally no later than 2028, after which we will begin to shift our focus to the potential launch of R289 in lower-risk MDS and other potential indications. Consistent with our prior transactions, we are prioritizing assets that leverage our existing commercial infrastructure, which will enable operational efficiency and thus be rapidly accretive and drive sustained cash generation for the company.

這些後期資產是目標機會，將在未來三年內推出，理想情況下不遲於 2028 年。之後，我們將開始把重點轉移到 R289 在低風險 MDS 和其他潛在適應症的潛在推出。與我們先前的交易一致，我們優先考慮能夠利用我們現有商業基礎設施的資產，這將提高營運效率，從而迅速增加公司收益並推動公司持續現金流。

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

接下來，我將把電話交給戴夫，讓他來討論我們發展商業業務的策略重點。戴夫？

Thank you, Raul. On slide 10, you'll see our three commercial products, TAVALISSE, GAVRETO and REZLIDHIA. Moving to slide 11. We are thrilled to report full year results for 2025 and how our net sales have consistently grown over the last five years. In 2021, TAVALISSE was the only product in our portfolio, and we generated $63 million in net sales.

謝謝你，勞爾。在第 10 張投影片上，您將看到我們的三款商業產品：TAVALISSE、GAVRETO 和 REZLIDHIA。切換到第11張投影片。我們很高興地宣布 2025 年全年業績，以及過去五年中我們的淨銷售額如何持續成長。2021 年，TAVALISSE 是我們產品組合中唯一的產品，我們實現了 6,300 萬美元的淨銷售額。

In 2022, we continued to grow TAVALISSE and brought REZLIDHIA into our portfolio, launching the product in December. In 2023, the addition of REZLIDHIA and continued growth of TAVALISSE propelled us over the $100 million annual sales threshold. Then in 2024, we continue to grow those sales and added our third brand, GAVRETO, to our portfolio.

2022 年，我們繼續發展 TAVALISSE，並將 REZLIDHIA 納入我們的產品組合，並在 12 月推出了該產品。2023 年，REZLIDHIA 的加入和 TAVALISSE 的持續成長推動我們突破了 1 億美元的年銷售額大關。隨後在 2024 年，我們繼續擴大銷售，並將第三個品牌 GAVRETO 加入我們的產品組合中。

And in 2025, we exceeded our expectations, delivering $232 million in net product sales, an increase of $87 million or 60% compared to 2024. This outstanding year over year growth was primarily driven by increased demand across our portfolio, which included the onetime favorable effect from increased patient affordability during the year and favorable gross-to-net dynamics, partially offset by lower inventory levels.

2025 年，我們超越了預期，淨產品銷售額達到 2.32 億美元，比 2024 年增加了 8,700 萬美元，增幅達 60%。這一顯著的同比增長主要得益於我們產品組合需求的增長，其中包括患者在年內支付能力提高帶來的一次性有利影響以及毛利淨利的有利變化，但部分被較低的庫存水平所抵消。

To summarize, our strategy of focusing on both product and portfolio growth over the last four years has nearly quadrupled our net sales. And over just the last two years, that growth has accelerated as we've more than doubled sales. Our strategy to grow our commercial business is working, and I want to thank the entire organization for collaborating as one Rigel team to create such outstanding results.

總而言之，過去四年我們專注於產品和產品組合成長的策略使我們的淨銷售額成長了近四倍。在過去的兩年裡，這種成長速度加快了，我們的銷售額翻了一番還多。我們發展商業業務的策略正在奏效，我要感謝整個組織像一個Rigel團隊一樣通力合作，創造瞭如此傑出的成果。

Slide 12 shows a summary of our fourth quarter commercial performance by product. For the fourth quarter, we generated a record $65.4 million, an increase of $18.9 million or 41% compared to the fourth quarter of 2024.

第 12 張投影片總結了我們第四季各產品的商業表現。第四季度，我們創造了創紀錄的 6,540 萬美元收入，比 2024 年第四季增加了 1,890 萬美元，增幅達 41%。

First on TAVALISSE, I'm pleased to report another record quarter in which we generated $45.6 million in net product sales, an increase of 47% compared to the fourth quarter of 2024. TAVALISSE was approved in 2018 and is our cornerstone product, now reaching $45 million in quarterly sales, a true achievement for the team. For GAVRETO, we delivered $10.2 million in net product sales, an increase of 27% compared to the fourth quarter of 2024. GAVRETO became commercially available from Rigel in mid-2024. And following the successful integration of this product, we were able to maintain the sales level that was generated in the prior company's hands, and we have now grown it to be a stable contributing product in our portfolio.

首先，關於 TAVALISSE，我很高興地報告，我們又迎來了一個創紀錄的季度，淨產品銷售額達到 4,560 萬美元，比 2024 年第四季成長了 47%。TAVALISSE 於 2018 年獲得批准，是我們的核心產品，目前季度銷售額達到 4500 萬美元，這對團隊來說是一項真正的成就。GAVRETO 的淨產品銷售額為 1,020 萬美元，比 2024 年第四季成長了 27%。GAVRETO 於 2024 年中期由 Rigel 公司正式上市。在成功整合該產品後，我們得以維持先前公司所創造的銷售水平，並且現在已將其發展成為我們產品組合中穩定的貢獻產品。

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

REZLIDHIA 的淨產品銷售額為 960 萬美元，比上年同期成長了 29%。自 2022 年引進該產品以來，其季度收入已增長至近 1000 萬美元，比一年前實現了大幅增長，我們相信未來還會有更大的增長。我們相信 REZLIDHIA 具有巨大的發展機遇，因為我們相信它在 IDH1 突變復發或難治性 AML 患者群體中具有重要的差異化優勢，即我們令人信服的數據證明了持久的療效，以及我們在難以治療的維奈托克後環境中的持續療效結果。

Finally, on slide 13, we generated $4.4 million in revenues from collaborations in the fourth quarter, driven by the availability of TAVALISSE in global markets. TAVALISSE is commercially available in Europe under the brand name TAVLESSE, in Japan and South Korea and Asia and in Canada and Israel via our partners, Grifols, Kissei and Medison.

最後，在第 13 張幻燈片中，由於 TAVALISSE 在全球市場的上市，我們在第四季度透過合作獲得了 440 萬美元的收入。TAVALISSE 在歐洲以 TAVLESSE 品牌名稱銷售，在日本、韓國和亞洲以及加拿大和以色列透過我們的合作夥伴 Grifols、Kissei 和 Medison 銷售。

Our partners continue to pursue regulatory approvals for TAVALISSE in new markets. And we continue to work on expanding access to our products in markets outside of the US For REZLIDHIA, in 2024, we expanded our relationship with Kissei to include several countries in Asia for all potential indications, and we entered into an exclusive license agreement with Dr. Reddy's for all potential indications throughout Dr. Reddy's territory.

我們的合作夥伴正在繼續努力，爭取TAVALISSE在新市場獲得監管部門的批准。我們將繼續努力擴大我們產品在美國以外市場的銷售管道。 2024 年，我們擴大了與 Kissei 的合作關係，將 REZLIDHIA 的合作範圍擴大到亞洲的幾個國家，涵蓋所有潛在適應症；此外，我們還與 Dr. Reddy's 簽訂了獨家許可協議，涵蓋 Dr. Reddy's 業務區域內的所有潛在適應症。

These partners are now in the process of advancing REZLIDHIA in preparation for future potential regulatory submissions. We are pleased that access to our products is expanding outside the US.

這些合作夥伴目前正在推動 REZLIDHIA 的研發，為未來可能的監管申報做準備。我們很高興看到我們的產品在美國以外的市場也越來越受歡迎。

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

現在我將把電話交給 Lisa，讓她報告我們開發流程的進度。麗莎？

Thanks, Dave. I will now provide an update on our progress over the last quarter and plans for the year ahead. I'm on slide 15. Our current hematology and oncology focus areas are the clinical development of R289, our potent and selective dual IRAK1 and IRAK4 inhibitor and our strategic collaborations with academic partners to evaluate olutasidenib in clinical settings beyond relapsed/refractory IDH1 mutated AML. Our Phase 1b study of R289 in patients with relapsed or refractory lower-risk myelodysplastic syndrome, or MDS, is progressing well and updated data from the dose escalation part of the study was recently presented in an oral session at ASH.

謝謝你，戴夫。接下來，我將報告上個季度的工作進度以及未來一年的計畫。我看到第15張投影片了。我們目前在血液學和腫瘤學領域的重點是 R289 的臨床開發，R289 是一種強效且選擇性的雙重 IRAK1 和 IRAK4 抑制劑；以及我們與學術合作夥伴的策略合作，以評估 olutasidenib 在復發/難治性 IDH1 突變 AML 以外的臨床環境中的療效。我們正在對複發或難治性低風險骨髓增生異常綜合徵（MDS）患者進行 R289 的 1b 期研究，目前進展良好，該研究劑量遞增部分的最新數據已於近期在 ASH 的口頭會議上公佈。

I'll provide an update on that study as well as our planned next steps for R289 shortly. For olutasidenib, we have a number of strategic collaborations to study olutasidenib in additional therapeutic areas. Through our collaboration with MD Anderson, olutasidenib is being evaluated in five clinical studies as monotherapy or combination therapy in patients with a variety of IDH1 mutation-positive hematologic malignancies, including AML, higher and lower-risk MDS, chronic myelomonocytic leukemia, or CMML, and its post-transplant maintenance therapy. In addition, a study of olutasidenib in combination with co-targeted therapy in patients with relapsed or refractory AML with additional signaling pathway mutations is underway.

我將盡快提供該研究的最新進展以及我們針對 R289 的下一步計劃。對於奧魯西地尼，我們進行了多項策略合作，以研究奧魯西地尼在其他治療領域的應用。透過與 MD 安德森癌症中心的合作，奧魯西地尼正在五項臨床研究中作為單藥療法或聯合療法，用於治療各種 IDH1 突變陽性的血液系統惡性腫瘤，包括 AML、高風險和低危險 MDS、慢性粒單核細胞白血病 (CMML) 及其移植後維持治療。此外，目前正在進行一項研究，評估奧魯西地尼聯合標靶治療對伴隨額外訊號路徑突變的複發或難治性 AML 患者的療效。

Our second collaboration with the CONNECT Cancer Consortium and the Phase 2 TarGeT-D study is evaluating olutasidenib in combination with temozolomide followed by olutasidenib monotherapy as maintenance treatment in newly diagnosed pediatric and young adult patients with IDH1 mutation-positive high-grade glioma.

我們與 CONNECT 癌症聯盟的第二次合作以及 2 期 TarGeT-D 研究正在評估奧魯西地尼聯合替莫唑胺治療，隨後奧魯西地尼單藥治療作為新診斷的 IDH1 突變陽性高級別膠質瘤兒童和年輕成人患者的維持治療。

First patient was enrolled in the study in October. Lastly, we're also partnering with the National Institutes of Health and National Cancer Institute's MyeloMATCH Precision Medicine Trial Initiative. The planned study will evaluate olutasidenib in first-line IDH1 mutated AML and MDS. We're excited about olutasidenib's potential to provide a new treatment option in these underserved patient populations and look forward to seeing the data that these studies generate in the future. Now I'll discuss R289, our novel dual IRAK1 and IRAK4 inhibitor.

首例患者於10月入組研究。最後，我們也與美國國立衛生研究院和國家癌症研究所的 MyeloMATCH 精準醫療試驗計畫合作。計畫中的研究將評估奧魯西地尼一線治療IDH1突變型AML和MDS的療效。我們對奧魯西地尼預計將為這些服務不足的患者群體提供新的治療選擇感到興奮，並期待在未來看到這些研究產生的數據。現在我將討論 R289，我們新型的雙重 IRAK1 和 IRAK4 抑制劑。

Let's start with the treatment landscape for lower-risk MDS. I'm now on slide 17. MDS is a clonal disorder of hematopoietic stem cells, leading to dysplasia and ineffective hematopoiesis. The main consequences for patients are anemia and transfusion dependence, which adversely impact their quality of life. In addition, infections, iron overload from transfusions and subsequent organ dysfunction all negatively impact the patient.

讓我們先來看看低風險 MDS 的治療現況。我現在看到第17張投影片了。MDS 是一種造血幹細胞克隆性疾病，會導致造血功能異常和無效造血。對患者的主要後果是貧血和輸血依賴，這會對他們的生活品質產生不利影響。此外，感染、輸血引起的鐵過量以及隨之而來的器官功能障礙都會對患者產生負面影響。

Therapies used in the upfront setting include erythropoiesis-stimulating agents, or ESAs, if patients are eligible or luspatercept. Luspatercept and more recently, imetelstat are also approved for ESA failure transfusion-dependent patients. Finally, while hypomethylating agents or HMAs are also approved, the percentage of patients achieving transfusion independence is low. With 8-week transfusion independence rates approaching 40% with luspatercept and imetelstat, there is still a need for safe, effective therapies for transfusion-dependent lower-risk MDS patients that are relapsed/refractory to or ineligible for ESAs.

第一線治療方案包括促紅血球生成素（ESA）（如果患者符合條件）或魯帕特西普。Luspatercept 和最近核准的 imetelstat 也已獲準用於治療 ESA 治療失敗的輸血依賴型患者。最後，雖然低甲基化藥物或 HMA 也已獲批准，但實現輸血獨立的患者比例很低。使用 luspatercept 和 imetelstat 治療 8 週後，輸血獨立率接近 40%，但對於復發/難治性或不適合接受 ESA 治療的輸血依賴型低危險群 MDS 患者，仍需要安全有效的治療方法。

On slide 18, you'll see the value proposition of R289 in lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the US. And as mentioned on the previous slide, there's a high unmet need for therapies in this disease area, particularly for transfusion-dependent patients. Dysregulation of inflammatory signaling is key to the pathogenesis of lower-risk MDS and IRAK1 and 4 mediate this process. Blocking both IRAK1 and 4 may suppress marrow inflammation and leukemic stem progenitor cell function and restore normal hematopoiesis. R835, the active moiety of R289, blocks toll-like receptor and IL-1 receptor signaling in vitro and was active in various preclinical models of inflammation.

在第 18 張投影片中，您將看到 R289 在低風險 MDS 中的價值主張。美國約有 12,000 名先前接受過治療的低風險 MDS 患者。正如上一張投影片所提到的，該疾病領域對治療的需求遠未得到滿足，尤其是對輸血依賴型患者而言。發炎訊號失調是低風險 MDS 發病機制的關鍵，IRAK1 和 4 介導此過程。同時阻斷 IRAK1 和 4 可能抑制骨髓發炎和白血病幹細胞祖細胞功能，並恢復正常的造血功能。R289 的活性部分 R835 可在體外阻斷 Toll 樣受體和 IL-1 受體訊號傳導，並在各種發炎的臨床前模型中具有活性。

Clinical proof of concept of this anti-inflammatory effect came from a healthy volunteer study in which R835 markedly suppressed LPS-induced cytokine release compared to placebo. As a reminder, R289, which is currently being evaluated in the clinic, is the oral prodrug that is rapidly converted to R835 in the gut. R289 has Fast Track designation for the treatment of patients with previously treated transfusion-dependent lower-risk MDS and orphan drug designation for MDS from the FDA, giving the molecule an expedited regulatory pathway, potential priority review and seven years of market exclusivity upon approval.

此抗發炎作用的臨床概念驗證來自一項健康志願者研究，該研究發現，與安慰劑相比，R835 能顯著抑制 LPS 誘導的細胞激素釋放。提醒一下，目前正在臨床評估的 R289 是一種口服前藥，可在腸道內迅速轉化為 R835。R289 獲得了美國食品藥物管理局 (FDA) 授予的快速通道資格，用於治療先前接受過治療的輸血依賴型低危險 MDS 患者，並被授予 MDS 孤兒藥資格，這使得該分子能夠獲得快速監管途徑、潛在的優先審查以及獲批後七年的市場獨佔權。

Both of these designations underscore the agency's interest in this rare disease, the unmet need of the patient population and the FDA's willingness to collaborate with Rigel in the development of R289. R289 has thus far demonstrated a promising clinical profile in our Phase 1b study with encouraging safety and preliminary efficacy data that were highlighted recently at ASH in December.

這兩項認定都凸顯了該機構對這種罕見疾病的關注，患者群體未被滿足的需求，以及 FDA 與 Rigel 合作開發 R289 的意願。到目前為止，R289 在我們的 1b 期研究中表現出了良好的臨床前景，其安全性和初步療效數據令人鼓舞，這些數據最近在 12 月的 ASH 會議上得到了重點介紹。

On slide 19, I'd like to quickly review the design of our multicenter open-label Phase 1b study in patients with relapsed/refractory lower-risk MDS, which aims to evaluate the safety, tolerability, PK and preliminary efficacy of R289 in this patient population as well as select a dose for future studies. The dose escalation phase evaluated six different R289 dosing regimens administered once or twice daily using a modified 3+3 design.

在第 19 張投影片中，我想快速回顧我們針對復發/難治性低風險 MDS 患者的多中心開放標籤 1b 期研究的設計，該研究旨在評估 R289 在該患者群體中的安全性、耐受性、藥物動力學和初步療效，並為未來的研究選擇劑量。劑量遞增階段採用改良的 3+3 設計，評估了每天一次或兩次給藥的六種不同的 R289 給藥方案。

In the dose expansion part of the study, up to 40 transfusion-dependent relapsed/refractory lower-risk MDS patients will be randomized to receive R289 doses of either 500 milligrams once or twice daily in order to select the recommended Phase 2 dose for future clinical studies. The first dose expansion patient was dosed in October. We anticipate that we will have sufficient data to make a decision on the recommended Phase 2 dose in the second half of this year.

在劑量擴展研究部分，將隨機選擇 40 名輸血依賴型復發/難治性低風險 MDS 患者，分別接受每日一次或兩次 500 毫克的 R289 劑量，以便為未來的臨床研究選擇建議的 2 期劑量。首例劑量擴展試驗患者於10月接受了給藥。我們預計今年下半年將有足夠的數據來決定建議的第二期臨床試驗劑量。

Once we've selected the dose, we will evaluate R289 in a cohort of less heavily pretreated patients who are relapsed/refractory to or ineligible for ESAs. Now I'd like to walk you through updated safety and efficacy results from the Phase 1b study with the data cutoff date of October 28 that were presented at ASH.

一旦我們確定了劑量，我們將對一組既往治療較少、對 ESA 治療無效或不適合接受 ESA 治療的患者進行 R289 評估。現在我想帶大家了解一下在 ASH 上公佈的 1b 期研究的最新安全性和有效性結果，數據截止日期為 10 月 28 日。

On slide 21, you will see the characteristics of the 33 patients enrolled in the dose escalation part of the study. The median age was 75 and the patients were heavily pretreated with a median of three prior therapies with around 70% having received prior luspatercept and HMAs. In addition, the majority of the patients had a high baseline transfusion burden. These characteristics are really representative of the lower-risk MDS population with the highest unmet medical need.

在第 21 張投影片中，您將看到參與劑量遞增研究的 33 名患者的特徵。患者年齡中位數為 75 歲，且先前接受過大量治療，平均接受過三種療法，其中約 70% 的患者曾接受過 luspatercept 和 HMA 治療。此外，大多數患者基線輸血負擔較重。這些特徵確實代表了低風險 MDS 族群，他們面臨最高的未滿足醫療需求。

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

接下來請看第 22 張投影片，我們將回顧安全調查結果。整體而言，R289 的耐受性良好，3 級或 4 級細胞減少症和感染的發生率較低。報告了一例劑量限制性毒性，即每日 750 毫克劑量下 AST/ALT 升高 3/4 級，其他劑量組均未發現劑量依賴性毒性的證據。

On slide 23, the swimmer plot shows an overview of transfusion events by dose group, starting with the lowest dose group, 250 milligrams daily at the top. Red cell transfusions occurring over 16 weeks prior to start of R289 are shown to the left of the colored bars, establishing the baseline transfusion frequency for each patient. All patients were transfusion dependent, except for two. The median time on therapy was 5.5 months, ranging from 0.9 months to nearly 28 months of treatment. To be evaluable for hematologic response assessment, patients must have been treated for at least 16 weeks. No response has occurred at 250 milligrams once or twice daily.

在第 23 張幻燈片上，游泳者圖顯示了按劑量組劃分的輸血事件概覽，從最低劑量組（每天 250 毫克）開始。在 R289 開始前 16 週內發生的紅血球輸注顯示在彩色條的左側，確定了每位患者的基線輸血頻率。除兩名患者外，所有患者均依賴輸血治療。治療的中位數時間為 5.5 個月，範圍從 0.9 個月到近 28 個月不等。要進行血液學反應評估，患者必須接受至少 16 週的治療。每天服用 250 毫克，一日一次或兩次，均未見療效。

Of 18 evaluable patients receiving dose levels of 500 milligrams daily or higher, six patients or 33% achieved red cell transfusion independence or RBC-TI, lasting for eight weeks or longer. In four patients, RBC-TI lasted for more than 16 weeks and for three patients for more than six months. The median duration of RBC-TI was around 23 weeks, ranging from nine weeks up to more than 24 months. Also, the median time to onset of RBC-TI was about two months, which is also encouraging. While this is a small data set, we're encouraged by these results given the highly refractory nature of these patients.

在接受每日 500 毫克或更高劑量治療的 18 名可評估患者中，有 6 名患者（佔 33%）實現了紅血球輸注獨立性（RBC-TI），持續時間為八週或更長時間。四名患者的 RBC-TI 持續時間超過 16 週，三名患者的 RBC-TI 持續時間超過 6 個月。RBC-TI 的中位數持續時間約為 23 週，範圍從 9 週到超過 24 個月。此外，RBC-TI 的中位發病時間約為兩個月，這也令人鼓舞。雖然這是一個小樣本資料集，但考慮到這些患者的難治性，我們對這些結果感到鼓舞。

Slide 24 presents a summary of the patients achieving RBC-TI. All patients had received two or more prior therapies, some had received experimental therapies and 5 of the 6 had received prior HMAs. For these patients, peak hemoglobin increases ranging from 2.9 to 6.1 grams per deciliter were also observed, indicating the potential of R289 to improve anemia. In summary, R289 was generally well tolerated with an encouraging safety profile and promising preliminary efficacy in an elderly, heavily pretreated lower-risk MDS patient population.

第 24 張投影片總結了達到 RBC-TI 的患者情況。所有患者都接受過兩種或兩種以上先前的治療，有些患者接受過實驗性治療，6 名患者中有 5 名接受過 HMA 治療。對於這些患者，也觀察到血紅素峰值增加範圍為每分升 2.9 至 6.1 克，顯示 R289 有改善貧血的潛力。總之，R289 在老年、接受過大量預處理的低危險 MDS 患者族群中整體耐受性良好，安全性令人鼓舞，且初步療效令人鼓舞。

On slide 25, I will review the next steps for R289. We aim to complete enrollment of the dose expansion phase of the study and selection of the recommended Phase 2 dose for future studies in the second half of this year. We anticipate sharing top line data from the dose expansion phase by the end of the year. Once the recommended Phase 2 dose has been selected, we will evaluate R289 in a cohort of less heavily pretreated patients who are relapsed/refractory to or ineligible for ESAs in the same study.

在第 25 張投影片中，我將回顧 R289 的後續步驟。我們的目標是在今年下半年完成該研究劑量擴展階段的受試者招募，並選擇未來研究的建議二期劑量。我們預計在年底前分享劑量擴展階段的主要數據。一旦確定了建議的 2 期劑量，我們將在同一項研究中，對一組既往治療較少、對 ESA 治療無效或不符合 ESA 治療條件的患者進行 R289 評估。

In addition, upon completion of the Phase 1b study, we plan to follow up with the FDA to discuss a potential registration study. With its mechanism of action, we believe that R289 has potential in other indications where the pro-inflammatory cascade plays a role, and we'll provide more details as our plans progress.

此外，在 1b 期研究完成後，我們計劃與 FDA 接洽，討論潛在的註冊研究。我們相信，憑藉其作用機制，R289 在其他涉及促發炎級聯反應的適應症中具有潛力，隨著我們計劃的推進，我們將提供更多細節。

Now turning to our partnered program with Eli Lilly. On slide 27, I'd like to provide a short update on ocadusertib, the non-CNS penetrant RIPK1 inhibitor previously referred to as R552 that is being evaluated in an adaptive Phase 2a/2b clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis. During the fourth quarter, enrollment in the Phase 2a part of the study was completed, and the trial is ongoing.

現在讓我們來看看我們與禮來公司的合作項目。在第 27 張投影片中，我想簡要介紹 ocadusertib，這是一種非中樞神經系統穿透性 RIPK1 抑制劑，以前被稱為 R552，目前正在一項適應性 2a/2b 期臨床試驗中進行評估，該試驗將招募多達 380 名患有活動性中度至重度類風濕性關節炎的患者。第四季度，研究的 2a 期部分受試者招募工作已完成，試驗正在進行中。

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

現在我把電話轉給迪恩，讓他來討論我們的財務狀況。院長？

Thank you, Lisa. I'm on slide number 29. We reported net product sales of $65.4 million for the fourth quarter, a growth of 41% year over year, including TAVALISSE net product sales of $45.6 million, a growth of 47% year over year, GAVRETO net product sales of $10.2 million a growth of 27% year over year. Lastly, we reported REZLIDHIA net product sales of $9.6 million, a growth of 29% year over year. Our net product sales were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance and other allowances of $19 million.

謝謝你，麗莎。我看到第29張投影片了。第四季淨產品銷售額為 6,540 萬美元，較去年同期成長 41%，其中 TAVALISSE 淨產品銷售額為 4,560 萬美元，較去年同期成長 47%；GAVRETO 淨產品銷售額為 1,020 萬美元，較去年同期成長 27%。最後，我們報告 REZLIDHIA 淨產品銷售額為 960 萬美元，年增 29%。我們的淨產品銷售額已扣除估計的折扣、退款、回扣、退貨、共同支付援助和其他補貼 1900 萬美元。

We also reported $4.4 million in contract revenues for the fourth quarter, primarily consisting of $3.4 million of revenue from Grifols related to the delivery of drug supplies and earned royalties, $300,000 of revenue from Kissei related to the delivery of drug supplies, $300,000 in government contract revenues and $200,000 of revenue from Medison related to earned royalties. This brings our total revenue for the fourth quarter to $69.8 million. Moving to slide 30. For the fourth quarter of 2025, our cost of product sales was approximately $6 million. Total costs and expenses were $46.6 million compared to $40.9 million for the same period in 2024.

我們還報告稱，第四季度合約收入為 440 萬美元，主要包括 Grifols 公司提供的藥品供應和已賺取的特許權使用費收入 340 萬美元，Kissei 公司提供的藥品供應收入 30 萬美元，政府合約收入 30 萬美元，以及 Medison 公司提供的已賺取的特許權使用費收入 20 萬美元。這使得我們第四季的總營收達到 6,980 萬美元。轉到第30張投影片。2025 年第四季度，我們的產品銷售成本約為 600 萬美元。總成本和費用為 4,660 萬美元，而 2024 年同期為 4,090 萬美元。

The increase in costs and expenses was mainly due to increased research and development costs, driven by the timing of clinical activities related to R289 and olutasidenib and higher personnel-related costs. Fourth quarter results include a nonrecurring income tax benefit driven by the release of the valuation allowance on our deferred tax asset.

成本和費用的增加主要是由於研發成本的增加，而研發成本的增加又是由與 R289 和 olutasidenib 相關的臨床活動的時間安排以及人員相關成本的增加所驅動的。第四季業績包含一項非經常性所得稅收益，該收益源自於我們遞延所得稅資產估值準備的釋放。

For reference, the valuation allowance is recorded against deferred tax assets when it's more likely than not that those assets will not be realized. Given our track record of profitability, projected operating income and positive outlook, we concluded that a release of the valuation allowance was appropriate as of December 31, 2025. While this release impacts reported GAAP net income and earnings per share, it does not affect our cash position or our day-to-day operating performance.

作為參考，當遞延所得稅資產很可能無法實現時，估價準備金會記入遞延所得稅資產的帳面。鑑於我們以往的獲利記錄、預計的營業收入和積極的前景，我們認為從 2025 年 12 月 31 日起釋放估值準備金是合適的。雖然此次發表會影響報告的 GAAP 淨收入和每股收益，但不會影響我們的現金狀況或日常經營業績。

In this context, for the fourth quarter, income before income taxes was $22.7 million compared to $15.2 million for the same period of 2024. Benefit from income taxes was $245.4 million in the fourth quarter, which was primarily driven by $245.9 million of noncash deferred income tax benefit, partially offset by state tax expenses. We reported net income of $268.1 million for the fourth quarter compared to $14.3 million for the same period in 2024. For the full year, cost of product sales was $19.6 million. Total costs and expenses were $168.8 million compared to $155.1 million for the full year of 2024.

在此背景下，第四季所得稅前收入為 2,270 萬美元，而 2024 年同期為 1,520 萬美元。第四季所得稅收益為 2.454 億美元，主要得益於 2.459 億美元的非現金遞延所得稅收益，部分被州稅支出抵銷。我們公佈的第四季淨收入為 2.681 億美元，而 2024 年同期淨收入為 1,430 萬美元。全年產品銷售成本為 1,960 萬美元。總成本和費用為 1.688 億美元，而 2024 年全年為 1.551 億美元。

The increase in cost and expenses was primarily due to increased research and development costs, driven by the timing of clinical activities related to R289 and olutasidenib, higher personnel-related costs and higher cost of product sales. Income before income taxes was $121.8 million for the year compared to $18.4 million for the full year of 2024.

成本和費用的增加主要是由於研發成本的增加（這是由於與 R289 和 olutasidenib 相關的臨床活動的時間安排所致）、人員相關成本的增加以及產品銷售成本的增加。該年度稅前收入為 1.218 億美元，而 2024 年全年稅前收入為 1,840 萬美元。

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

本年度所得稅收益為 2.452 億美元，主要得益於 2.459 億美元的非現金遞延所得稅收益，部分被州稅支出抵銷。我們公佈的全年淨收入為 3.67 億美元，而 2024 年全年淨收入為 1,750 萬美元。截至年底，我們的現金、現金等價物和短期投資為 1.55 億美元，而截至 2024 年底，這一數字為 7,730 萬美元。

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

接下來是我們對2026年的財務展望。我們預計總收入約為 2.75 億美元至 2.9 億美元，其中淨產品銷售額約為 2.55 億美元至 2.65 億美元，合約收入約為 2,000 萬美元至 2,500 萬美元。我們也預計全年將實現正淨收入，同時為現有和新的臨床開發項目提供資金。

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

總之，2025 年對 Rigel 來說是收入大幅成長並維持財務紀律的一年。我們將繼續努力實現成長策略的關鍵組成部分，力爭實現 2026 年的財務目標。

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

那麼，我想把電話交還給勞爾。勞爾？

Thank you, Dean. Moving on to slide 31 as we wrap up. Our key strategic objectives for 2026 are clear: grow our commercial business, pursue in-license opportunities to further expand our portfolio and thus enhance cash generation, advance our development pipeline, particularly R289 and maintain financial discipline as we deliver another year of top line growth and positive net income. We are especially excited about our opportunity for R289. This year includes several anticipated milestones in lower-risk MDS, including dose expansion phase data expected at the end of the year.

謝謝你，院長。接下來，我們來看第 31 張投影片，結束今天的分享。我們 2026 年的主要策略目標很明確：發展我們的商業業務，尋求引進許可機會以進一步擴大我們的產品組合，從而增強現金流，推進我們的研發管線，特別是 R289，並在實現又一年營收成長和淨利潤為正的過程中保持財務紀律。我們對R289計畫的機會感到格外興奮。今年低風險 MDS 領域將迎來幾個預期的里程碑，包括預計在年底公佈的劑量擴展階段數據。

In addition, we are evaluating additional opportunities for R289, and we look forward to sharing further updates later in the year. In closing, the focused execution against our four strategic objectives has driven transformational growth since 2020 and culminated in a record performance in 2025. We believe this momentum positions us well for a strong 2026 as reflected in our financial guidance and for the continued value creation the rest of this decade.

此外，我們正在評估 R289 的其他機會，並期待在今年稍後分享更多最新消息。總之，自 2020 年以來，我們專注於執行四大策略目標，實現了變革性成長，並在 2025 年取得了創紀錄的業績。我們相信，這一發展勢頭將使我們在 2026 年取得強勁業績（正如我們的財務預期所反映的那樣），並有助於我們在本十年剩餘時間裡持續創造價值。

With that, I will turn the call over to the operator for questions. Operator, we're now ready for questions.

接下來，我將把電話轉交給接線員，解答大家的問題。接線員，我們現在可以開始接受提問了。

(Operator Instructions)

（操作說明）

Joe Pantginis, H.C. Wainwright.

喬·潘特吉尼斯，H.C. 溫賴特。

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

首先，我們來談談已核准的產品成長。那麼，當您審視 TAVALISSE 時，鑑於這是一個相對成熟的產品，您認為目前有哪些因素可以推動其成長？至於 GAVRETO，正如你所描述的，它顯然是一個穩定的貢獻產品。我想這樣問：重新引入 GAVRETO 的努力將如何促進其潛在成長？

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

謝謝你，喬。我會請戴夫就這兩個問題發表意見。

Yeah. Thanks for the question, Joe. Obviously, last year was an incredible year of growth with TAVALISSE. It was our single largest year of growth ever. And as I said, it was in my prepared remarks, demand was a driver of our growth for all of our products last year.

是的。謝謝你的提問，喬。顯然，去年對TAVALISSE來說是成長迅猛的一年。這是我們有史以來成長幅度最大的一年。正如我在事先準備好的演講稿中所說，去年需求是我們所有產品成長的驅動力。

But I will say that, that was helped by a onetime favorable effect from increased affordability, which means that the elimination of the coverage gap happened last year. And with that came an ability for patients with Medicare Part D to have improved affordability to move on to TAVALISSE. So that helped certainly last year, but that was a onetime effect. And then obviously, we won't see that kind of effect happening in future years. But we're going to do what we've always done with TAVALISSE, which is continue to grow new patient starts.

但我要說的是，這得益於經濟承受能力提高帶來的一次性有利影響，這意味著醫保缺口的消除發生在去年。因此，參加 Medicare Part D 的患者能夠以更實惠的價格使用 TAVALISSE。所以這在去年確實起到了一定的作用，但這只是一次性的效果。很顯然，未來幾年我們不會看到這種效應再次發生。但我們將像以往一樣對待 TAVALISSE，繼續增加新患者的入組人數。

Look, Joe, it's a market of more than 14,000 patients in the second line and later setting. There's a number of treatment options out there, but a lot of doctors treat ITP. And so our goal is to make sure we get to them with the message that TAVALISSE is an outstanding alternative for patients. They can take this drug and it can keep their platelet levels where a clinician and the patient wants to have them and they can go on living their life. And so what we try to do is to spread that message as far wide as possible.

聽著，喬，這是一個擁有超過 14,000 名二線及後續治療患者的市場。目前有很多治療方案，但很多醫生都會治療 ITP。因此，我們的目標是確保我們向他們傳達這樣的訊息：TAVALISSE 是患者的傑出選擇。他們可以服用這種藥物，使他們的血小板水平保持在臨床醫生和患者希望達到的水平，這樣他們就可以繼續正常生活。因此，我們努力將這項訊息盡可能廣泛地傳播出去。

We've done some things last year that were very good to spread that message like even we piloted a virtual sales team because that's both efficient and it's effective in kind of generating messages further than your -- your field team, and we saw some really good results with that. So those are the kinds of things we're going to focus on in 2026 and beyond to continue to grow new patients starts with TAVALISSE. We think that's really important. And then with GAVRETO, I think, as I said, in the prior company's hands, this was about a $28 million to $30 million product, and we generated over $40 million last year. And we think that's just great.

去年我們做了一些非常好的事情來傳播這一訊息，例如我們甚至試行了一個虛擬銷售團隊，因為這既高效又有效，可以比你的現場團隊更廣泛地傳播訊息，而且我們看到了一些非常好的結果。因此，這些就是我們在 2026 年及以後要重點關注的事情，以繼續吸引新患者，而 TAVALISSE 正是實現這一目標的起點。我們認為這非常重要。至於 GAVRETO，正如我之前所說，在前一家公司手中，這大概是一款價值 2800 萬至 3000 萬美元的產品，而我們去年創造了超過 4000 萬美元的收入。我們認為這真是太棒了。

It shows -- and a big part of our growth, right, was having GAVRETO for a full year versus just a half a year in 2024. Obviously, we're not going to have that advantage in 2026, but it shows how our strategy of in-licensing and acquisition is working. And so we'll continue some very targeted efforts there. We think there's some great opportunities with GAVRETO that we're going to continue to do. And as we've always done, try as hard as we can to continue growing our portfolio sales year over year.

事實證明——我們取得巨大成長的一個重要原因，就是 GAVRETO 能夠持續一整年，而 2024 年只有半年。顯然，到 2026 年我們就不會有這種優勢了，但這顯示我們引進許可和收購的策略是有效的。因此，我們將繼續在那方面進行一些有針對性的工作。我們認為 GAVRETO 蘊藏著一些絕佳的機會，我們將繼續掌握這些機會。和以往一樣，我們會盡一切努力，逐年提高我們的產品組合銷售。

Yigal Nochomovitz, Citi.

Yigal Nochomovitz，花旗集團。

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

我剛喝了幾杯。我對您關於劑量方面的決定很感興趣，500 毫克/天還是 500 毫克/天，您覺得哪種方案更適合您？這兩種方案的優缺點是什麼？根據你目前掌握的所有信息，你覺得哪種可能性更大？那麼，關於BD在收購其他資產方面有什麼想說的嗎？我知道你肯定一直在關注各種事情，而且有很多東西需要消化，才能找到最適合你——適合你業務的東西。所以，您能否就此事進展發表一下看法？

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

謝謝你，伊加爾。我會請 Lisa 對劑量發表意見，至於 BD 的問題，我會回答。

Thanks, Raul. Thanks for the question, Yigal. So at the time we selected the doses for comparison in dose expansion, and we wanted to be compliant with the FDA's Project Optimus. So we do the most robust dose selection possible. We compared the lowest effective dose, which was 500 milligrams daily with the highest safe dose at that time was 500 milligrams BID.

謝謝你，勞爾。謝謝你的提問，伊加爾。因此，當時我們選擇了劑量擴展比較的劑量，並且我們希望符合 FDA 的「優化項目」的要求。因此，我們採取了最穩健的劑量選擇方法。我們將最低有效劑量（每日 500 毫克）與當時最高的安全劑量（每日兩次 500 毫克）進行了比較。

So I think that we don't really have a preference where we'll see what unfolds with the data. One could think that with BID dosing, you may have more tonic suppression of inflammation instead of kind of peaks and troughs. So that's one factor in favor of the BID potentially. But since both doses were active, as you saw with the ASH data, we're going to wait this one out.

所以我覺得我們沒有特別的偏好，我們會看看數據會如何發展。人們可能會認為，採用每日兩次給藥的方式，可以更好地抑制炎症，而不是出現高峰和低谷。所以這可能是對商業改進提案有利的因素。但正如你在 ASH 數據中看到的那樣，由於兩種劑量都有效，我們將拭​​目以待。

Yigal, on your second question, we are looking at a great number of opportunities out there in hematology/oncology. And we're in a fortunate place that many opportunities that are out there are in the order of magnitude in terms of the size that would be appropriate for us. And we're evaluating a multitude of opportunities on a constant basis. The difficulty is projecting exactly when one will fall into place and we get to a yes and we sign the deal. But when you have enough balls in the air, one eventually does fall into place.

Yigal，關於你的第二個問題，我們正在尋找血液學/腫瘤學領域的大量機會。我們很幸運，目前有很多機會的規模都非常適合我們。我們一直在評估各種機會。困難在於準確預測何時時機成熟，雙方達成協議並簽署協議。但是，當你同時處理足夠多的事情時，總是會有一個事情最終得到解決。

We succeeded in acquiring GAVRETO a couple of years ago in '24, and we succeeded acquiring REZLIDHIA couple of years before that in '22. So '26 is a year that we hope to accomplish this. If not, we certainly would make a big effort to try to get it done. Like I said, we're looking for late-stage opportunities that are about ready to launch that is NDA ready or NDA filed or already approved, where a company of our size and our scale of business could add value to the launch of the product. And there's a number of things out there that look attractive for us. And so we're continuously work towards that, and we'll tell you exactly when it is when we have a press release related to this.

我們在 2024 年成功收購了 GAVRETO，在此之前的 2022 年，我們成功收購了 REZLIDHIA。所以，我們希望在2026年實現這個目標。如果不行，我們一定會盡力爭取完成這件事。正如我所說，我們正在尋找處於後期階段、即將上市、已準備好提交新藥申請、或已提交新藥申請或已獲批准的產品機會，像我們這樣規模和業務範圍的公司可以為產品的上市增添價值。而且，有很多東西看起來都很吸引我們。因此，我們一直朝著這個方向努力，一旦有相關的新聞稿發布，我們會第一時間告訴大家。

Ashleigh Acker, Piper Sandler.

阿什利·阿克，派珀·桑德勒。

This is Ashleigh. I'm on for Ally Bratzel at Piper Sandler. So I just had one on R289. So we know you're launching the exploratory study in post ESA or treatment-naive MDS. We know that this represents a really significant earlier line population.

這是阿什利。我代表 Piper Sandler 出戰 Ally Bratzel。我剛剛在 R289 上遇到了一個。所以我們知道您正在進行一項針對 ESA 治療後或未經治療的 MDS 患者的探索性研究。我們知道這代表了一個非常重要的早期品系群。

So can you just remind me what the strategic rationale is for exploring this population now rather than waiting for a registrational trial? And also, what kind of benefit are you aiming to show in this population? Anything that you're able to frame in terms of response rates or durability? Just to have us thinking about this would be really helpful.

那麼，您能否提醒我一下，為什麼現在就對這一人群進行研究，而不是等待註冊試驗？此外，您希望為該人群帶來哪些益處？有什麼可以就響應速度或耐用性進行分析的嗎？能讓我們思考這個問題真的很有幫助。

Thanks for the question, Ashleigh. This is Lisa. So -- the reason that we're going to do that is because we -- if you think about that treatment landscape slide that I talked through, we are now in patients that are more heavily pretreated, high transfusion burden. So this is a really unique population where we started compared to the other agents on the market that, for example, luspatercept and imetelstat. So they generated their data in a patient population that were more or less post ESA or ineligible for ESA transfusion-dependent patients.

謝謝你的提問，阿什利。這是麗莎。所以——我們這樣做的原因是——如果你想想我剛才講解的治療現況幻燈片，我們現在面對的是接受過更多預處理、輸血負擔沉重的患者。因此，與其他市場上的藥物（例如 luspatercept 和 imetelstat）相比，我們研究的這個族群非常獨特。因此，他們收集的數據來自那些或多或少已經接受 ESA 治療或不符合 ESA 輸血依賴條件的患者群體。

So we started here. We're very encouraged by the data that we're seeing thus far, given the refractory nature of the patients. And we have -- we're optimistic that as we move the drug into an earlier line of therapy, that activity may be even better. So this is in the plans. Once we get the recommended Phase 2 dose, that's why we want to open that cohort of the less heavily pretreated patients to evaluate 289 in that patient population and get some preliminary data.

所以我們就從這裡開始。考慮到患者的難治性，我們對目前為止看到的數據感到非常鼓舞。我們樂觀地認為，隨著我們將這種藥物引入更早期的治療方案，其療效可能會更好。所以這已經列入計劃了。一旦我們獲得建議的 2 期劑量，這就是為什麼我們希望開放這群預處理較少的患者群體，以評估 289 在該患者群體中的效果並獲得一些初步數據。

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

關於你的第二個問題，正如你——正如 Lisa 所說，目前獲批的產品確實存在局限性，luspatercept 和 imetelstat 在相當早期的患者中的反應率為 38%、40%，HMA 的反應率為 18% 至 20%。就能夠提供益處的產品而言，這裡還有很多需要改進的地方。而像 289 這樣作用機制與所有這些藥物都截然不同的藥物，我們認為對於低風險 MDS 患者來說將是一個真正的福音。正如你所聽到的，麗莎，在我們接受測試的患者中，約有 33% 的患者需要輸血 500 毫克以上才能進行療效評估。雖然病例數仍然很少，但對於難治性患者來說，這是一個相當不錯的早期結果。因此我們樂觀地認為，我們可能會獲得更廣泛的好處，特別是如果我們更早採取行動，特別是考慮到目前還沒有一個我們無法改進的、那麼有吸引力的指標。

Farzin Haque, Jefferies.

Farzin Haque，傑富瑞集團。

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

我有一對。就像 289 號疫苗一樣，你們在劑量擴展階段的招募工作進展如何？在尋找患者方面是否遇到任何挑戰？那麼，您能否說明在與監管機構會面商討下一步方案之前，您需要多少後續工作？

Okay. Thanks for the question, Farzin. I'll take that. So the enrollment is progressing. As I mentioned, we are aiming to select the recommended Phase 2 dose in the second half of the year, and we're on track to do that. In terms of the follow-up that we would need as before to be eligible for evaluation of red cell transfusion independence, the patients should have been treated for at least 16 weeks before we can make that determination. So it's going to be a combined look at PK safety and efficacy data in terms of recommended Phase 2 dose selection.

好的。謝謝你的提問，法爾津。我接受。所以招生工作正在順利進行中。正如我之前提到的，我們的目標是在今年下半年確定建議的第二階段劑量，目前我們正按計劃推進。就後續追蹤而言，為了符合評估紅血球輸注獨立性的條件，我們需要對患者進行至少 16 週的治療，然後才能做出該決定。因此，我們將綜合考慮藥物動力學安全性和有效性數據，以確定建議的 2 期劑量選擇。

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

知道了。然後，就淨產品銷售額預期而言，考慮到我們在 2025 年看到的成長，這個預期似乎有點保守。該展望是否考慮了任何特定的庫存變化、競爭逆風或保守的市場准入假設？

Yeah, that's a good question, Farzin, and I'll be happy to take that. Listen, as I said, we're just absolutely thrilled that we just grew $87 million, generating $232 million last year. And as I said in my prepared remarks, that was driven by demand growth across all the brands, and it was helped by a onetime favorable effect from improved patient affordability during the year and favorable gross to net dynamics. And as I just said, you should recall that we had GAVRETO for the full year versus half a year in 2024. And so we had just a phenomenal year, and you put everything together, and that's what generated $87 million or 60% growth.

是的，法爾津，你問得好，我很樂意回答這個問題。正如我所說，我們非常高興我們剛剛實現了 8700 萬美元的成長，去年總收入達到了 2.32 億美元。正如我在準備好的發言稿中所說，這是由所有品牌的需求增長推動的，並且得益於患者在這一年中支付能力的提高以及毛利淨利動態的有利影響。正如我剛才所說，你應該記得，2024 年我們全年都有 GAVRETO 的比賽，而 2024 年只有半年。因此，我們度過了非常出色的一年，把所有因素加在一起，就產生了 8700 萬美元或 60% 的成長。

So moving to 2026. I'm telling you, we're really quite pleased to announce that on top of that really strong and very remarkable growth last year, we're still expecting double-digit growth. So we wouldn't call that a low expectation, but rather a challenging one, given that we're working off a much higher base now with all three brands and we don't have that onetime favorable effect of improved affordability. And we won't know -- we improved gross to net so much last year that it's really going to be difficult to have that kind of impact again in 2026. We still work on it, but there are things that are out of your control as well.

所以時間延到2026年。我告訴你，我們非常高興地宣布，在去年強勁且顯著的成長基礎上，我們仍然預計今年將實現兩位數的成長。所以，考慮到我們現在所有三個品牌的基數都高得多，而且我們也沒有了價格實惠帶來的那種有利影響，因此我們不會稱之為低期望，而是一個具有挑戰性的期望。我們無從得知——去年我們的毛利與淨利潤之比大幅提升，因此在 2026 年再次取得同樣的成就將非常困難。我們仍在努力，但有些事情也是我們無法控制的。

So look, here's what we have to do. We've got to continue to drive new patient starts with TAVALISSE after it just generated its single largest year of growth ever in its history. And we have to realize this outstanding opportunity we still believe we have with REZLIDHIA. And those are big challenges for us as an organization, but we think we have the ability to do that. So again, I would say we're actually setting high expectations after a very remarkable year, and we'll work every single day to try to achieve those expectations. But I certainly wouldn't call them muted by any stretch of the imagination.

所以，我們得這樣做。我們必須繼續推動 TAVALISSE 的新患者入組，因為該藥物剛剛實現了其歷史上最大的單年增長。我們必須意識到，我們仍然相信，我們與 REZLIDHIA 擁有這一絕佳的機會。這些對我們組織來說都是巨大的挑戰，但我們認為我們有能力應對這些挑戰。所以，我想再次強調，在經歷了非常出色的一年之後，我們實際上設定了很高的期望，我們將每天努力實現這些期望。但我絕對不會用任何理由稱他們沉默寡言。

I would have to agree with you, Dave. The onetime effects of last year got us to a very different level than we had ever been historically. And this level, we're maintaining and building on into this year. It's not going to be the outstanding growth over last year. It's going to be incremental growth in the double digits, but it's not going to be like 60%.

我同意你的看法，戴夫。去年的一次性事件使我們達到了一個與歷史上任何時期都截然不同的水平。今年，我們將保持並提升這一水平。不會像去年那樣實現顯著成長。將會是兩位數的漸進式增長，但不會像 60% 那麼高。

That's not the case. The patient affordability helped a lot last year, though it's still affordable this year. That is beneficial to us. So we're going to maintain those level of sales and plan to growing those. One thing I should note is because we got to this level of sales last year and again, this year, it means we're profitable. That's a fantastic place to be, generating cash as a business, and we have a great place to invest that cash in terms of opportunities like R289 that I think are truly transformational.

事實並非如此。去年患者負擔能力的提高起到了很大的幫助，儘管今年仍然負擔得起。這對我們有利。所以我們將保持目前的銷售水平，並計劃實現成長。需要指出的是，我們去年和今年都達到了這樣的銷售水平，這意味著我們已經獲利了。這是一個非常棒的地方，可以創造現金流，而且我們還有很好的地方可以投資這些現金，像是像 R289 這樣我認為真正具有改變意義的機會。

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

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

大部分問題都已經問過了，不過鑑於你們在過去一年左右的時間裡收入大幅增長，我或許可以問問銷售團隊的一位成員，你們是否有計劃加大對銷售團隊的投入，進一步擴大規模？或者您覺得，現在大多數醫生都對您的工作有了相當清晰的了解，並且與您有足夠的接觸？

Yeah. So great question, Kristen. Listen, we look at the impactability of all of our brands consistently. We look at where we have the most opportunity to grow. And certainly, our sales force has been pivotal to spreading the word about TAVALISSE, REZLIDHIA and making sure people understood that it's now available -- that GAVRETO is now available for Rigel.

是的。克里斯汀，你問得真好。聽著，我們會持續關注我們所有品牌的影響力。我們會尋找最具發展潛力的領域。當然，我們的銷售團隊在宣傳 TAVALISSE、REZLIDHIA 並確保人們了解它現在可用——GAVRETO 現在可用於 Rigel 方面發揮了關鍵作用。

And so we focus them on where the opportunity is. And certainly, we're constantly looking at whether we're having the right promotional effectiveness out there in the field. But we think we're rightsized. We're calling on the right clinicians. We've got a lot of data.

因此，我們將他們的注意力集中在機會所在的地方。當然，我們也一直在關注我們在實際推廣活動中是否取得了應有的效果。但我們認為我們的規模正合適。我們正在聯繫合適的臨床醫生。我們有很多數據。

That's one of the areas that we've really improved on over the last several years, but particularly last year, we've really had a strong emphasis on really looking at our data sources and really understanding where the best opportunities are to generate business. And we've even incorporated some very innovative tools to target where that business is. So I think we're well positioned on our sales team to realize the opportunities that are out there. But it is challenging to access clinicians. I'll say that.

這是我們在過去幾年中真正取得進步的領域之一，但尤其是在去年，我們非常重視認真審視我們的資料來源，並真正了解哪裡有最好的商機。我們甚至融入了一些非常創新的工具，以精準定位目標業務所在。所以我認為，我們的銷售團隊已經做好充分準備，能夠抓住市場上的機會。但要聯絡到臨床醫師卻很困難。我會這麼說。

Over and over again, I mean, our team is superb at it, but it is not easy, and it just gets harder to access clinicians. So that's why we really focus on kind of where the business opportunity is. If there's an IDH1 patient there, that's where we're going with the REZLIDHIA message. And we're really trying to be very, very thoughtful about where we can provide impact with a message like that. So to answer your question, we're not looking at expanding the sales organization at this point in time. As a matter of fact, we're looking at ways to make sure we're even more impactful with the resources we have.

我的意思是，我們的團隊在這方面非常出色，但這並不容易，而且接觸臨床醫生也越來越難。所以這就是為什麼我們真正關注的是商機所在。如果那裡有 IDH1 患者，那就是我們向他發送 REZLIDHIA 訊息的目標。我們正在非常認真地思考，如何讓這樣的訊息產生影響。所以回答你的問題，我們目前沒有擴大銷售組織的計畫。事實上，我們正​​在研究如何更有效地利用現有資源，並發揮更大的影響力。

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

目前沒有其他問題了。我想把電話轉回給勞爾·羅德里格斯先生。

Thank you very much, operator. Everyone, thank you for joining us on the call today and for your continued interest in Rigel. I'd also like to take the opportunity to thank our employees for their ongoing dedication. Their innovation, integrity and steadfast commitment to patients has driven our evolution as a company and has expanded access to important therapies for those living with hematology and oncology conditions.

非常感謝接線生。各位，感謝你們今天參加我們的電話會議，也感謝你們一直以來對Rigel的關注。我還要藉此機會感謝我們員工一直以來的奉獻。他們的創新精神、誠信和對患者的堅定承諾推動了我們公司的發展，並擴大了血液疾病和腫瘤患者獲得重要療法的機會。

2025 was a tremendous year for Rigel, marked by strong growth in our commercial portfolio, advancement of our development pipeline and a solid financial position. These traits put us in a favorable and very select position within the biotech industry, and we look forward to updating you on our continued progress. Thank you, and have a good evening.

2025 年對 Rigel 來說是意義非凡的一年，我們的商業產品組合實現了強勁增長，研發管線取得了進展，財務狀況也十分穩健。這些特質使我們在生技產業中處於有利且非常獨特的地位，我們期待向您報告我們持續取得的進展。謝謝，祝您晚安。

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

今天的電話會議到此結束。您可以在此時斷開線路。感謝您的參與。