Rigel Pharmaceuticals Inc (RIGL) 2024 Q4 法說會逐字稿

Greetings, and welcome to Rigel Pharmaceuticals financial conference call for the fourth quarter and full year 2024. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Rigel Pharmaceuticals 2024 年第四季和全年財務電話會議。（操作員指示）提醒一下，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.

現在我很高興介紹我們的第一位演講者，Rigel 的執行副總裁、總法律顧問兼公司秘書 Ray Furey。謝謝你，弗瑞先生。你可以開始了。

Welcome to our fourth quarter and full year 2024 financial results and business update conference call. The financial press release for the fourth quarter and 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.

歡迎參加我們的 2024 年第四季和全年財務表現和業務更新電話會議。2024 年第四季和全年的財務新聞稿剛剛發布，您可以在 rigel.com 的投資者關係網站「新聞和活動」部分中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 on our most recent Annual Report on Form 10-K for the year ended December 31, 2024, on file with the SEC. 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.

提醒一下，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計劃和時間做出前瞻性陳述。這些聲明受風險和不確定性的影響，可能導致實際結果與預測結果不同。這些風險的描述可以在我們向美國證券交易委員會提交的截至 2024 年 12 月 31 日的最新年度報告（表格 10-K）中找到。任何前瞻性陳述僅截至今日作出，我們不承擔更新這些前瞻性陳述以反映後續事件或情況的義務。

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

現在，我想將電話轉給我們的總裁兼執行長 Raul Rodriguez。勞爾？

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.

謝謝你，雷，也謝謝大家今天的到來。今天和我一起的還有我們的首席商務官戴夫·桑托斯 (Dave Santos)；我們的首席醫療官 Lisa Rojkjaer；以及我們的首席財務官 Dean Schorno。

Beginning on slide 4, 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 collaborations; and third, maintaining financial discipline.

從第 4 張投影片開始，我們將概述 Rigel 的業務以及我們在 2024 年取得的眾多成就。對於剛加入公司的人，請允許我花點時間回顧一下 Rigel 發展血液學和腫瘤學業務的整體公司策略。我們的策略集中在三個主要目標：第一，擴大我們的商業組合併增加產品銷售；第二，透過內部開發和策略合作來推進和擴大我們的產品線；第三，保持財務紀律。

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.

2024 年對 Rigel 來說是轉型之年，因為我們實現了所有這三個目標。我將向你更詳細地介紹每一項成就。

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. This significant revenue growth was driven by the strength of TAVALISSE and REZLIDHIA 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.

2024年，我們再創銷售新高。由於我們有效的商業執行，我們的商業投資組合銷售額達到了有史以來最高的 1.45 億美元，比 2023 年增長了 39%。這一顯著的收入增長得益於 TAVALISSE 和 REZLIDHIA 銷售的強勁增長，以及我們的第三款產品和第二個授權產品 GAVRETO 的加入，自我們 6 月份將其添加到我們的產品組合以來，該產品貢獻了 1,710 萬美元的淨產品銷售額。

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, Knight and Kissei announced regulatory approvals for TAVALISSE in two new countries, Mexico and the Republic of Korea, respectively. Once commercially launched, ITP patients in these countries can also benefit from TAVALISSE. For REZLIDHIA, we actively pursued new collaborations and executed new license agreements with our partner, Kissei, in three countries in Asia and with Dr. Reddy for numerous territories outside of the US

我們也從 TAVALISSE 商業化的合作夥伴那裡獲得了收入，並且我們的合作夥伴繼續在擴大 TAVALISSE 在其他地區的使用方面取得進展。最近，Knight 和 Kissei 分別宣佈在墨西哥和韓國這兩個新國家批准 TAVALISSE。一旦商業化推出，這些國家的 ITP 患者也可以從 TAVALISSE 中受益。對於 REZLIDHIA，我們積極尋求新的合作，並與我們的合作夥伴 Kissei 在亞洲三個國家簽訂了新的許可協議，並與 Dr. Reddy 在美國以外的眾多地區簽訂了新的許可協議

Also in 2024, on our second goal, we made significant progress in our development pipeline. We continue to evaluate R289, our dual IRAK1/4 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 on new sixth dose level at 500 milligrams BID.

同樣在 2024 年，我們在實現第二個目標方面取得了重大進展。我們將繼續在正​​在進行的 1b 期研究中評估我們的雙重 IRAK1/4 抑制劑 R289 對低風險 MDS 患者的作用。我們在 12 月的 ASH 年會上展示了該研究令人鼓舞的初步安全性和有效性數據。參與試驗劑量遞增部分，我們最近完成了第五個劑量水平，現在已開始招募新的第六個劑量水平（每日兩次，每次 500 毫克）。

For olutasidenib, our strategic collaborations with MD Anderson and CONNECT organization continue to progress. These trials provide us with the opportunity to explore olutasidenib 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 multiyear strategic development alliance with MD Anderson have now opened for enrollment.

對於奧魯替尼，我們與 MD Anderson 和 CONNECT 組織的策略合作正在繼續推進。這些試驗為我們提供了以省時省錢的方式探索奧魯他尼在一系列 IDH1 突變癌症中的作用的機會。我們很高興地報告，我們與 MD Anderson 建立的多年策略發展聯盟的所有四項研究現已開放招生。

And the Phase 2 study of olutasidenib in high-grade glioma in collaboration with CONNECT has also recently opened for enrollment. Lisa will provide you an update on these development programs in a few minutes.

而與CONNECT合作的奧魯他尼治療高惡性度膠質瘤的2期研究也已於近期開放患者入組。幾分鐘後，Lisa 將為您提供這些開發計劃的最新進展。

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, 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.

最後，2024 年我們的第三個目標是維持財務紀律。透過保持財務紀律，我們首次實現了 1700 萬美元的全年淨收入，並且全年現金餘額增加了 2000 多萬美元。所有這些成就使 Rigel 能夠繼續成功實施我們的策略。

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% between 2021 and 2024. TAVALISSE grew nicely over that period and the addition of REZLIDHIA in late '22 and GAVRETO in 2024 has provided additional contributions to that growth. All three of these products achieved new highs in 2024.

繼續下一張投影片。我們的淨產品銷售額持續成長，2021 年至 2024 年期間的複合年增長率為 32%。TAVALISSE 在此期間發展良好，而 2022 年底加入 REZLIDHIA 和 2024 年加入 GAVRETO 也為這一增長做出了額外貢獻。這三種產品均在2024年創下新高。

And in 2025, as you can see on slide 6, we're expecting approximately [$185 million] (corrected by company after the call) to $192 million in net product sales for the year, approximately a 28% to 32% growth compared to 2024. 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.

到 2025 年，正如您在第 6 張投影片上看到的那樣，我們預計全年淨產品銷售額約為 [1.85 億美元]（電話會議後公司進行了更正）至 1.92 億美元，與 2024 年相比增長約 28% 至 32%。總而言之，2024 年是轉型之年，我們將繼續發展血液學和腫瘤學業務，同時成為一家獲利的公司。

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

說完這些，我會把電話轉給戴夫，讓他提供商業更新。戴夫？

Thank you, Raul. On slide 8, you'll see our three commercial products, TAVALISSE, REZLIDHIA and GAVRETO. We are very pleased with the strong growth in revenues in the fourth quarter and full year of 2024.

謝謝你，勞爾。在第 8 張投影片上，您將看到我們的三種商業產品：TAVALISSE、REZLIDHIA 和 GAVRETO。我們對2024年第四季和全年營收的強勁成長感到非常高興。

Moving to slide 9, 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. That growth has been driven by our strong commercial execution in consistently building quarterly demand for TAVALISSE and driving broader awareness of REZLIDHIA through the first two years of its launch.

翻到第 9 張投影片，您可以看到自 2021 年以來我們的季度和年度銷售額的變化。我們每季的銷售額都比前一年有所成長，而且這種成長趨勢還在持續，特別是從去年到今年。2023 年第一季我們的營業收入為 2,380 萬美元，目前報告指出 2024 年第四季我們的營業收入為 4,650 萬美元。這一增長得益於我們強大的商業執行力，在 TAVALISSE 推出後的頭兩年內持續提升季度需求，並提高 REZLIDHIA 的知名度。

In addition, our ability to successfully and seamlessly transition GAVRETO into our portfolio has significantly expanded our top line. 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.

此外，我們成功且無縫地將 GAVRETO 過渡到我們的產品組合的能力顯著擴大了我們的營收。與 2023 年第四季相比，我們在 2024 年第四季實現了 58% 的成長。2024 年全年，我們實現了創紀錄的近 1.45 億美元的收入，與 2023 年 1.04 億美元的淨銷售額相比增長 4,100 萬美元，增幅為 39%。

Our commercial team has been dedicated to execution, driving continued momentum for TAVALISSE and improving both institutional and community demand for REZLIDHIA and successfully transitioning GAVRETTO patients and accounts to Rigel label product.

我們的商業團隊一直致力於執行，推動 TAVALISSE 的持續發展勢頭，提高機構和社區對 REZLIDHIA 的需求，並成功地將 GAVRETTO 患者和帳戶過渡到 Rigel 標籤產品。

My sincere thanks to the entire team for all their hard work to grow our business in 2024.

我衷心感謝整個團隊為 2024 年業務成長所做的一切努力。

Slide 10 shows a summary of our commercial performance by product. First, on TAVALISSE, 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 TAVALISSE demand through both refills from patients who stay on the product and new prescriptions for patients who are starting TAVALISSE for the first time.

投影片 10 顯示了我們按產品劃分的商業表現摘要。首先，關於 TAVALISSE，我很高興地報告我們又一個強勁的季度，本季度我們實現了 3,100 萬美元的淨產品銷售額，與 2023 年第四季度相比增長了 21%。這一成長是由強勁的患者需求推動的，連續一個季度創下歷史新高。我們透過繼續使用該產品的患者的續藥和首次開始使用 TAVALISSE 的患者的新處方來繼續增加 TAVALISSE 的需求。

Moving to REZLIDHIA. We reported $7.4 million in net product sales, almost doubling revenue from the prior year period as we focus on improving REZLIDHIA adoption, both in institutions and the community by raising awareness of REZLIDHIA's efficacy particularly in patients who have failed upfront therapy with venetoclax.

移至 REZLIDHIA。我們報告的淨產品銷售額為 740 萬美元，幾乎是去年同期收入的兩倍，因為我們專注於透過提高人們對 REZLIDHIA 療效的認識（特別是對於使用 venetoclax 進行前期治療失敗的患者），來提高機構和社區對 REZLIDHIA 的採用率。

And lastly, for GAVRETO. 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 GAVRETO's upward trajectory during last year's transition and are now focused on building on that momentum in 2025.

最後，感謝 GAVRETO。在我們銷售該產品的第二個完整季度中，我們在第四季度實現了 810 萬美元的淨產品銷售額。我們對 GAVRETO 患者、處方人員和帳戶成功轉移到 Rigel 分銷網絡感到非常高興。重要的是，我們第四季 810 萬美元的淨產品銷售額代表著高於 GAVRETO 在先前所有權下 2023 年 2,800 萬美元的年銷售額的運作率。我們對 GAVRETO 在去年轉型期間的上升軌跡感到特別高興，現在我們專注於在 2025 年繼續保持這一勢頭。

Moving to slide 11. We hit several meaningful milestones with our portfolio in 2024. Importantly, for TAVALISSE, 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 bottles shipped to patients in clinics. That steady growth has been driven by more new patients starting on TAVALISSE each quarter and the subsequent increased carryover that's generated.

移至投影片 11。2024 年，我們的投資組合達到了幾個有意義的里程碑。重要的是，對於 TAVALISSE 來說，2024 年是其淨銷售額首次超過 1 億美元的一年。作為我們產品組合的基礎，它繼續穩步增長，運送給診所患者的瓶子數量不斷創下季度新高。這種穩定的成長是由每季開始使用 TAVALISSE 的新患者增加以及隨之而來的結轉率增加所推動的。

In 2025, we expect that trend to continue. REZLIDHIA more than doubled both bottles shipped to patients in clinics as well as net sales in 2024. And we believe we still have significant opportunity to grow REZLIDHIA's use in mutant IDH1 relapsed or refractory acute myeloid leukemia.

到 2025 年，我們預計這一趨勢將持續下去。2024 年，REZLIDHIA 運送給診所患者的藥品數量和淨銷售額均增加了一倍以上。我們相信，我們仍有很大機會擴大 REZLIDHIA 在突變 IDH1 復發或難治性急性骨髓性白血病的應用。

We continue to find that as clinicians become more aware of REZLIDHIA'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 REZLIDHIA's use in 2025.

我們不斷發現，隨著臨床醫生越來越意識到 REZLIDHIA 對維奈克拉治療後患者的療效，他們認為它具有臨床意義，因為這些患者很難用其他療法治療。我們相信，我們可以利用目前在這一重要 AML 患者群體中可用的科學數據，並在 2025 年繼續擴大 REZLIDHIA 的使用。

Lastly, in 2024, our successful transition of GAVRETO 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 and quickly generated $17.1 million of incremental net sales in 2024.

最後，2024年，我們對GAVRETO的成功轉型展現了我們靈活且高度適應的組織能力。我們充分利用我們的商業和醫療事務基礎設施和專業知識，大幅擴展我們的血液學和腫瘤學產品組合，並在 2024 年迅速實現了 1710 萬美元的增量淨銷售額。

The Q4 GAVRETO 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 TAVALISSE and REZLIDHIA while that transition was ongoing is a testament to our organizational capabilities and operational efficiency.

GAVRETO 第四季淨銷售額達 810 萬美元，進一步證明新舊患者的過渡非常順利且有效。此外，在轉型期間，我們還能夠顯著發展 TAVALISSE 和 REZLIDHIA，這證明了我們的組織能力和營運效率。

In 2025, we can continue to grow GAVRETO, particularly since the use of RET inhibitors in non-small cell lung cancer should continue to expand in the frontline setting. 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 GAVRETO will grow in turn.

2025 年，我們可以繼續發展 GAVRETO，特別是因為 RET 抑制劑在非小細胞肺癌一線治療中的使用應該會繼續擴大。美國國家綜合癌症網絡 (NCCN) 於 1 月發布的新的非小細胞肺癌治療指南建議，如果一線治療中未使用 RET 抑制劑，一旦確認 RET 融合，臨床醫生可以將一線治療轉換為 RET 抑制劑。我們相信，2025年及以後，RET抑制劑在非小細胞肺癌的應用將會擴大，而GAVRETO也將隨之成長。

Finally, moving to slide 12. We're incredibly excited about our work to expand access to our patients in markets outside of the US. TAVALISSE is commercially available in Japan, in Europe under the brand name TAVLESSE and in Canada and Israel via our partners, Kissei, Grifols and Medison, and that's generating sustainable revenues each quarter. In addition, our partners continue to pursue regulatory approvals for TAVALISSE in new markets.

最後，轉到第 12 張投影片。我們對擴大美國以外市場患者治療管道的工作感到非常興奮。TAVALISSE 在日本、歐洲以品牌名稱 TAVLESSE 銷售，並透過我們的合作夥伴 Kissei、Grifols 和 Medison 在加拿大和以色列銷售，並且每個季度都能產生可持續的收入。此外，我們的合作夥伴繼續尋求 TAVALISSE 在新市場的監管批准。

As Raul mentioned, Knight Therapeutics announced it has received regulatory approval for TAVALISSE in Mexico. And recently, Kissei announced regulatory approval for TAVALISSE in Korea. In 2024, we also look to find partners to develop and commercialize REZLIDHIA in ex-US markets. We expanded our relationship with Kissei to include Japan, Korea, and Taiwan for REZLIDHIA in all potential indications.

正如 Raul 所提到的，Knight Therapeutics 宣布已獲得墨西哥監管部門對 TAVALISSE 的批准。最近，Kissei 宣布韓國監管部門批准 TAVALISSE。2024 年，我們也希望尋找合作夥伴在美國以外市場開發和商業化 REZLIDHIA。我們擴大了與 Kissei 的合作關係，將 REZLIDHIA 的所有潛在適應症擴展到日本、韓國和台灣。

And in late 2024, we entered into an exclusive license agreement with Dr. Reddy's for REZLIDHIA in all potential indications throughout Dr. Reddy's territory, which includes Latin America and other territories. We are pleased that access to our products is expanding outside the US, and we continue to explore other opportunities for partnerships outside the US to bring our products to other markets and patients around the globe.

2024 年底，我們與 Dr. Reddy's 簽訂了獨家授權協議，授權 REZLIDHIA 在 Dr. Reddy's 的整個地區（包括拉丁美洲和其他地區）的所有潛在適應症中使用。我們很高興看到我們的產品在美國以外的市場不斷擴大，我們也將繼續探索在美國以外建立合作的機會，將我們的產品推向全球其他市場和患者。

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

我現在將把電話轉給麗莎，讓她提供有關我們開發流程的最新資訊。麗莎？

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.

謝謝，戴夫。我們在 2024 年取得了重大進展，並期待在 2025 年繼續執行擴大血液學和腫瘤學產品組合的策略。

I'm on slide 14. First, from our development pipeline, R289 is our novel dual IRAK1/4 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.

我在第 14 張投影片。首先，從我們的開發流程來看，R289 是我們新型的雙重 IRAK1/4 抑制劑，目前正在針對復發/難治性低風險骨髓增生異常症候群 (MDS) 患者進行 1b 期研究評估。我們很高興 R289 被 FDA 授予快速通道資格，用於治療先前接受過輸血治療的低風險 MDS 患者，並被授予 MDS 孤兒藥資格。

Furthermore, as part of Rigel-sponsored development programs and alongside our partners, MD Anderson and the CONNECT Cancer Consortium, olutasidenib is being evaluated in new indications. We believe olutasidenib has potential in several cancers where mutated IDH1 plays a role, such as glioma, additional AML segments and MDS, either as monotherapy or in combination. We expect to initiate a Rigel-sponsored Phase 2 study to evaluate olutasidenib in recurrent glioma in 2025.

此外，作為 Rigel 贊助的開發項目的一部分，並與我們的合作夥伴 MD Anderson 和 CONNECT 癌症聯盟一起，對 olutasidenib 的新適應症進行評估。我們相信，奧魯他尼在多種由 IDH1 突變引起的癌症中都具有治療潛力，例如神經膠質瘤、其他 AML 片段和 MDS，無論是作為單一療法還是聯合療法。我們預計將於 2025 年啟動一項由 Rigel 贊助的 2 期研究，以評估奧魯他尼在治療復發性膠質瘤方面的作用。

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. 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 olutasidenib and pralsetinib, our goal is to continue to find assets that align with our organization pipeline and ability to execute.

此外，正如 Raul 所提到的，我們與 MD Anderson 合作進行的所有四項臨床試驗現在都已開放招募，專注於高級別膠質瘤的 CONNECT 研究也是如此。我們也將繼續專注於評估獲得許可或收購符合我們產品組合策略的產品的潛在機會。我們正在尋找血液學、腫瘤學或相關領域的差異化產品，這些產品處於後期階段，可能具有註冊數據，即將擁有註冊數據或更先進的產品，以及可以利用我們的血液學和腫瘤學基礎設施的產品。正如我們對 olutasidenib 和 pralsetinib 的收購所表明的那樣，我們的目標是繼續尋找與我們的組織管道和執行能力相符的資產。

Now I'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 in lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the US. 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.

現在我將花一些時間討論我們的 R289 計劃的更新。為了幫助組織討論，投影片 16 概述了 R289 在低風險 MDS 中的價值主張。美國約有 12,000 名接受過治療的低風險 MDS 患者。低風險 MDS 的最新開發工作主要集中在一線療法。然而，對於下一線療法的需求仍然很高，特別是對於先前接受過治療的輸血依賴患者。

Dysregulation of inflammatory signaling is key to the pathogenesis of lower-risk MDS and IRAK1/4 mediate this process. Blocking both IRAK1/4 may suppress marrow inflammation and leukemic stem and progenitor cell function and restore hematopoiesis. R835, the active moiety of R289, blocks toll-like receptor, and IL-1 receptor signaling in vitro and was active in various preclinical models of inflammation. Clinical proof of concept of this anti-inflammatory effect came from a healthy volunteer study in which R835 markedly suppressed LPS-induced cytokine release compared to placebo.

發炎訊號失調是低風險 MDS 發病機制的關鍵，而 IRAK1/4 則介導此過程。阻斷 IRAK1/4 可能抑制骨髓發炎和白血病幹細胞和祖細胞功能並恢復造血。R835 是 R289 的活性部分，可在體外阻斷 Toll 樣受體和 IL-1 受體訊號傳導，並在各種臨床前發炎模型中活躍。這種抗發炎作用的臨床概念證明來自一項健康志願者研究，其中與安慰劑相比，R835 顯著抑制了 LPS 誘導的細胞激素釋放。

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 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. 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.

提醒一下，目前正在臨床評估的 R289 是一種口服前驅藥物，可在腸道中快速轉化為 R835。R289 同時擁有 FDA 快速通道和孤兒藥資格，為該分子提供了快速監管途徑、潛在的優先審查以及獲批後七年的市場獨佔權。這兩項指定都強調了該機構對這種罕見疾病的興趣以及他們與 Rigel 合作開發 R289 的意願。

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.

此外，R289 迄今在 1b 期研究中表現出良好的初步臨床特性。今天的電話會議將審查最近在 ASH 年會上提出的初始劑量遞增數據。

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

在第 17 張投影片上，您可以看到低風險 MDS 的治療前景。MDS 是一種造血幹細胞克隆性疾病，導致造血幹細胞發育不良和無效造血。對患者來說，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、輸血導致的鐵超載以及隨後的器官功能障礙都會對患者產生負面影響。

Aside from transfusions, initial therapies include erythropoiesis stimulating agents, or ESAs, if patients are eligible and luspatercept. Imetelstat was approved earlier this year for ESA failure, high transfusion burden, lower-risk MDS. With eight-week transfusion independence rates approaching 40% with luspatercept and imetelstat, many patients require an alternative treatment option. Although hypomethylating agents, or HMAs, are approved, the percentage of patients achieving transfusion independence is low. Therefore, there is a high unmet need for safe, effective treatment options following failure of approved therapies, particularly for previously treated transfusion-dependent patients.

除了輸血之外，初始治療還包括紅血球生成刺激劑（ESA，如果患者符合條件）和luspatercept。Imetelstat 於今年稍早獲得批准，用於治療 ESA 失敗、高輸血負擔、低風險 MDS。使用 luspatercept 和 imetelstat 治療後，八週輸血獨立率接近 40%，許多患者需要替代治療方案。儘管低甲基化劑（HMA）已獲批准，但實現輸血獨立的患者比例仍然很低。因此，在已批准的療法失敗後，對安全、有效的治療方案的需求很高，特別是對於先前接受過治療的輸血依賴患者。

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 MDS patients with either symptomatic anemia or transfusion dependence. The study was recently updated to include a sixth dose level, 500 milligrams BID, and to facilitate the randomized comparison of two dose levels and expansion to optimize selection of the recommended Phase 2 dose.

在第 18 張投影片上，您將看到我們正在進行的針對患有症狀性貧血或輸血依賴的複發/難治性低風險 MDS 患者的開放標籤劑量遞增劑量擴展 1b 期研究的設計。該研究最近進行了更新，包括第六個劑量水平，即每日兩次 500 毫克，以便於隨機比較兩個劑量水平並進行擴展，以優化選擇建議的 2 期劑量。

The primary endpoints are safety and selection of the recommended dose for expansion and secondary endpoints include transfusion independence, hematologic improvement, response rates, and PK. The study continues to progress well with the sixth dose level 500 milligrams BID now open for enrollment. 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.

主要終點是安全性和選擇建議的擴增劑量，次要終點包括輸血獨立性、血液學改善、反應率和 PK。這項研究進展順利，第六個劑量水準 500 毫克 BID 現已開放招募。一旦確定了建議的 2 期劑量，一線低風險 MDS 患者的探索性隊列將開放以評估 R289 在早期治療中的應用。

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 aged 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 luspatercept.

現在我想向大家介紹一下最近在 ASH 年會上公佈的初始劑量遞增數據。在第 19 張投影片上，我們從患者特徵開始。報告了 22 名患者的數據，數據截止日期為 2024 年 10 月 25 日。患者平均年齡為76歲，約60%的患者年齡在75歲或以上。先前接受治療的中位數為三種，範圍從 1 到 8 種，超過 70% 的患者接受過 HMA 或 luspatercept 治療。

The majority of patients, 73% were high transfusion burden at baseline. The median time on therapy was 4.6 months. In summary, these were elderly, heavily pretreated patients with a high transfusion burden at baseline.

大多數患者（73%）在基線時輸血負擔較高。治療的中位數時間為4.6個月。總之，這些都是年老、接受過大量治療的患者，基線時輸血負擔很重。

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.

轉到投影片 20，我們將回顧安全發現。R289 整體耐受性良好。20% 或更多患者中最常見的治療出現的不良事件（幻燈片上未顯示）是腹瀉和疲勞，其次是發冷、噁心和瘙癢，均為 1 級或 2 級。

The most frequent Grade 3 or 4 adverse events with two events each where anemia, platelet count decreased, pneumonia and alanine aminotransferase or ALT increased. 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-milligram daily dose level. 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.

最常見的 3 級或 4 級不良事件為貧血、血小板計數減少、肺炎和丙氨酸氨基轉移酶或 ALT 升高，各發生兩起。幻燈片上顯示了與治療相關的不良事件。重要的是，對於該患者群體，3/4 級血球減少症和感染的發生率較低。報告了一種劑量限制性毒性，一名患者在每日劑量 750 毫克時出現 3/4 級轉氨酶升高。兩名或兩名以上患者發生的嚴重不良事件為肺炎和上消化道出血，均發生在兩名患者身上，且與治療無關。

On slide 21, we show the preliminary efficacy data. The swimmer plot shows each patient and the red cell transfusions by dose group, starting with the lowest dose group, 250 milligrams daily on top. Per the IWG 2018 criteria, the transfusion history for each patient was collected for 16 weeks prior to R289 administration to establish the baseline transfusion frequency, shown to the left of day zero indicated by the red arrow.

在投影片 21 上，我們展示了初步療效數據。游泳圖顯示了每位患者按劑量組進行的紅血球輸注情況，從最低劑量組開始，每天 250 毫克。根據 IWG 2018 標準，在 R289 給藥前 16 週收集每位患者的輸血史，以確定基線輸血頻率，如紅色箭頭所示，顯示在第零天的左側。

Two patients, numbers 9 and 19 were not transfusion dependent at baseline. 18 patients were evaluable for efficacy, meaning that they had one or more R289 doses and at least one efficacy assessment. Red blood cell transfusion independence lasting eight weeks or longer was achieved by three patients, one receiving 500 milligrams daily and two receiving 750 milligrams daily.

兩名患者（第 9 名和第 19 名）在基線時並不依賴輸血。 18 名患者可進行療效評估，這意味著他們接受過一次或多次 R289 治療，並且至少進行過一次療效評估。三名患者實現了持續八週或更長時間的紅血球輸注獨立性，其中一名患者每天接受 500 毫克，兩名患者每天接受 750 毫克。

In two patients, RBC transfusion independence lasted for more than 6 months, and 1 patient also achieved a marrow complete response. The median duration of transfusion independence was 29 weeks. One high transfusion burden patient receiving 500 milligrams daily achieved a minor HI-E response with a 64% reduction in red blood cell transfusions compared to baseline.

兩名患者的紅血球輸注獨立性持續了 6 個月以上，一名患者也實現了骨髓完全反應。輸血獨立性的中位數持續時間為29週。一名輸血負擔較重的患者每天接受 500 毫克治療，出現了輕微的 HI-E 反應，與基線相比，紅血球輸血量減少了 64%。

Regarding PK, at doses at or higher than 500 milligrams once daily, R835 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, hematologic responses occurred in 4 out of 10 or 40% of evaluable transfusion-dependent patients.

關於 PK，當劑量為每日一次 500 毫克或更高時，R835 血漿濃度達到或超過了先前在健康志願者中觀察到的 50% 或 90% LPS 誘導的細胞因子抑制相關的濃度。我們認為有趣的是，在這些劑量下，10 名可評估的輸血依賴患者中有 4 名或 40% 出現了血液學反應。

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 luspatercept, hypomethylating agents and some experimental therapies. The two patients with durable transfusion independence lasting more than six months, patients 4 and 10 were both high transfusion burden at baseline and had received HMAs.

在第 22 張投影片上，我們看到了對有反應的患者的總結。大多數患者在基線時輸血負擔較重，並且接受過多種治療，包括luspatercept、低甲基化藥物和一些實驗性療法。兩名患者能夠持久地脫離輸血依賴超過六個月，即患者 4 和患者 10，他們在基線時輸血負擔都很高，並且都接受了 HMA。

Beneath the table are the hemoglobin levels over time for the three patients that achieved transfusion independence. Peak hemoglobin increases ranging from 2.3 grams 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.

表格下方是三名實現輸血獨立的患者的血紅素水平隨時間的變化。與基線相比，峰值血紅蛋白增加了 2.3 克至 5.6 克/分升，顯示 R289 具有糾正貧血的潛力，為在治療早期進行評估提供支持。

In summary, the initial data is encouraging, showing R289 is generally well tolerated with promising signs of efficacy in heavily pretreated transfusion-dependent patients. Now I'll shift focus to olutasidenib, our IDH1 inhibitor.

總之，初步數據令人鼓舞，顯示 R289 通常耐受性良好，並且對接受過大量輸血治療的依賴性患者有良好的療效跡象。現在我將重點轉移到我們的 IDH1 抑制劑奧魯他尼。

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 US 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.

從第 24 張投影片開始，神經膠質瘤是一個極具挑戰性的領域，其治療方案尚未取得太大進展。瀰漫性膠質瘤是成人最常見的原發性腦瘤，每年在美國約有 20,000 人患病。約 70% 的 2 級和 3 級膠質瘤患者會出現 IDH1 突變，而多達近 40% 的年輕患者會出現這種突變。

Unfortunately, most disease recurs and there is no standard of care therapy for relapsed patients. The recent approval of vorasidenib, an IDH1 and 2 inhibitor in Grade 2 gliomas has highlighted the potential for IDH inhibitors in glioma.

不幸的是，大多數疾病都會復發，並且對於復發患者沒有標準的治療方案。沃拉西尼（Vorasidenib）是一種用於治療 2 級膠質瘤的 IDH1 和 2 抑制劑，最近獲得批准，凸顯了 IDH 抑制劑在治療膠質瘤方面的潛力。

Olutasidenib was previously evaluated in a Phase I1b/2 study in 26 patients, which was published in The Journal of 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 olutasidenib in glioma.

奧魯他地尼先前已在 26 名患者中進行了 I1b/2 期研究評估，研究結果發表在《神經腫瘤學雜誌》上。兩例高惡性度膠質瘤患者獲得部分緩解，均出現腫瘤增強，10 例患者病情穩定，疾病控制率 48%。此臨床概念驗證支持進一步評估奧魯他尼在治療膠質瘤中的作用。

Moving to slide 25. Last year, we entered a collaboration with the Global Neuro-Oncology Consortium CONNECT. In CONNECT's TarGeT trial, a molecularly guided Phase 2 umbrella clinical trial for high-grade glioma, the Rigel-sponsored arm of the study, TarGeT-D, will evaluate the post-radiotherapy maintenance regimen of olutasidenib in combination with temozolomide, followed by olutasidenib monotherapy in newly diagnosed patients between 12 and 39 years of age with IDH1 mutation positive high-grade glioma. This study was recently opened for enrollment.

移至第 25 張投影片。去年，我們與全球神經腫瘤學聯盟 CONNECT 建立了合作關係。在 CONNECT 的 TarGeT 試驗中，一項針對高級別膠質瘤的分子引導 2 期傘狀臨床試驗，由 Rigel 贊助的研究分支 TarGeT-D 將評估奧魯他尼聯合替莫唑胺的放療後維持方案，隨後對年齡在 12 至 39 歲之間的新診斷 IDH1 突變陽性高級別膠質瘤患者進行陽性高級別尼藥。這項研究最近已開始招募參與者。

In addition, we recently announced that this year, we plan to initiate a Phase 2 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 olutasidenib's potential to provide a much needed new treatment option to this underserved patient population, and we look forward to the data generation from the CONNECT study in addition to our planned study in recurrent glioma.

此外，我們最近宣布，我們計劃今年啟動復發性膠質瘤的 2 期臨床研究，我們期待在今年稍後提供有關該研究的更多細節。我們認為這是一個重要的機會，因為該患者群體中存在大量未滿足的醫療需求。我們和 CONNECT 一樣，對奧魯他尼為這一醫療資源匱乏的患者群體提供急需的新治療選擇的潛力感到興奮，並且除了我們計劃的複魯性膠質瘤研究之外，我們還期待 CONNECT 研究的數據生成。

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

在第 26 張投影片上，您將看到另一項重要的合作，即我們與 MD 安德森癌症中心的戰略聯盟，以將奧魯他尼更廣泛地應用於 AML、MDS 及其他領域。我們很高興地報告，此次合作中涉及的四項研究現已開放報名。

Turning to our partnered 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.

轉向我們的合作計劃。在投影片 28 上，我們與合作夥伴禮來公司的 RIPK1 抑制劑專案進展順利。RIPK1 與多種發炎細胞過程有關，並在腫瘤壞死因子訊號傳導中發揮關鍵作用。

Ocadusertib, 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. Our preclinical CNS penetrant RIPK1 inhibitor program is also progressing toward lead candidate nomination.

Ocadusertib 是我們的非中樞神經系統滲透性 RIPK1 抑制劑，之前稱為 R552，目前正在對多達 380 名活動性中度至重度類風濕性關節炎患者進行適應性 2a/2b 期臨床試驗。階段 2a 約 100 名患者的招募進展順利，預計將在 2025 年上半年對結果進行初步分析。我們的臨床前中樞神經系統滲透性 RIPK1 抑制劑計畫也朝著主要候選藥物提名的方向發展。

In closing, as you see on slide 29, there are several upcoming milestones for our development programs in 2025. For our R289 program in lower-risk MDS, we expect to complete the dose escalation portion of the Phase 1b study. The new six dose level, 500 milligrams twice daily is actively enrolling. We then plan to initiate the dose expansion phase later this year.

最後，正如您在第 29 張投影片上看到的，我們的 2025 年發展計畫即將實現幾個里程碑。對於低風險 MDS 的 R289 項目，我們預計將完成 1b 期研究的劑量遞增部分。新的六種劑量水平（每日兩次，每次 500 毫克）正在積極招募。我們計劃在今年稍後啟動劑量擴展階段。

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. Then for olutasidenib, we plan to initiate a Phase 2 clinical study in recurrent glioma by year-end, and also plan to provide you with more details about that study later this year.

此外，我們計劃在今年內尋求衛生部門對 R289 註冊途徑的意見，並預計將在今年下半年提交 1b 期研究的劑量遞增數據。對於奧魯他尼，我們計劃在年底前啟動復發性膠質瘤的 2 期臨床研究，並計劃在今年稍後向您提供有關該研究的更多詳細資訊。

In addition, we'll continue to support the four MD Anderson studies and CONNECT study. 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.

此外，我們將繼續支持四項 MD Anderson 研究和 CONNECT 研究。我們對 2024 年在推進這些計劃方面取得的進展感到非常興奮，並期待在 2025 年提供有關這些計劃里程碑的進一步更新。

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

現在，我將把電話轉給 Dean，討論本季的財務表現。

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 TAVALISSE net product sales of $31 million, a growth of 21% year over year; REZLIDHIA net product sales of $7.4 million, growth of 92% year over year; and GAVRETO net product sales of $8.1 million in the fourth quarter. As a reminder, GAVRETO became available for Rigel in June of 2024.

謝謝你，麗莎。我在第 31 張投影片。我們報告第四季淨產品銷售額為 4,650 萬美元，年增 58%，其中 TAVALISSE 淨產品銷售額為 3,650 萬美元，年增 21%； REZLIDHIA 淨產品銷售額為 740 萬美元，年增 92%； GAVRETO 第四季度淨產品銷售額為 810 萬美元。提醒一下，GAVRETO 將於 2024 年 6 月在 Rigel 上市。

Our net product sales from TAVALISSE, REZLIDHIA, and GAVRETO were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance, and other allowances of $19.7 million. For the fourth quarter of 2024, our gross to net adjustment for TAVALISSE, REZLIDHIA, and GAVRETO 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.

我們從 TAVALISSE、REZLIDHIA 和 GAVRETO 獲得的淨產品銷售額扣除了估計折扣、退款、回扣、退貨、共同支付援助和其他津貼後為 1,970 萬美元。2024 年第四季，我們對 TAVALISSE、REZLIDHIA 和 GAVRETO 的毛淨額調整分別約為總產品銷售額的 33%、21% 和 23%。我們第四季度的收入反映了強勁的患者需求，並且得益於我們過去看到的分銷管道年底庫存的增加。

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 TAVALISSE that would result in continued high-quality access while reducing our distribution costs and favorably impacting our gross to net adjustment into the future. While this change is not expected to impact our bottles shipped to patients in clinics, we expect to experience a reduction in bottles remaining in our distribution channel of approximately 350 bottles during the first quarter of 2025.

正如我們過去所看到的那樣，我們預計 2025 年第一季我們的分銷管道中的庫存水準將會下降。我們在第四季度強調，我們對 TAVALISSE 的分銷管道安排進行了一些改變，這將有助於繼續提供高品質的訪問，同時降低我們的分銷成本，並對我們未來的總淨額調整產生有利影響。雖然這項變更預計不會影響我們運送給診所患者的瓶子，但我們預計 2025 年第一季我們分銷管道中剩餘的瓶子數量將減少約 350 瓶。

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 collaborations for the fourth quarter, primarily driven by Grifols and Kissei along with $4 million in revenue from Dr. Reddy's related to the upfront fee from sublicensing of olutasidenib.

我們預計這些分銷管道的影響將在第一季末恢復正常。我們還報告了第四季度來自合作的合約收入 1,110 萬美元，主要來自 Grifols 和 Kissei，以及來自 Dr. Reddy's 的 400 萬美元收入，與 olutasidenib 再授權的預付費用有關。

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 costs and expenses were $40.9 million compared to $33.8 million for the same period of 2023.

進入下一張投影片，將損益表向下移動到成本和費用。2024 年第四季度，我們的產品銷售成本約為 580 萬美元。總成本和費用為 4,090 萬美元，而 2023 年同期為 3,380 萬美元。

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 asset, and sublicensing revenue fees.

成本和費用的增加主要是由於我們的臨床活動時間安排導致的研發成本增加、人員相關成本增加以及商業相關活動增加。此外，產品銷售成本增加主要由於產品銷售增加、特許權使用費增加、無形資產攤提增加、再授權收入費用。

For the full year, cost of product sales were approximately $18.6 million. Total costs and expenses were $155.1 million compared to $137.4 million for the full year of 2023. The increase in costs 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 sublicensing revenue fees.

全年產品銷售成本約 1,860 萬美元。總成本和費用為 1.551 億美元，而 2023 年全年為 1.374 億美元。成本和費用的增加主要是由於產品銷售成本增加，這主要受到產品銷售增加、特許權使用費增加、無形資產攤提增加以及再授權收入費用的影響。

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 IRAK1/4 inhibitor program, as well as reduced trial activities related to completed Phase 3 clinical trials during 2023.

此外，人員相關成本、股票薪酬費用和商業相關費用均有所增加。這些增長被研發成本的減少部分抵消，原因是與 R289（我們的雙重 IRAK1/4 抑制劑計劃）相關的臨床試驗活動的時間安排以及與 2023 年完成的 3 期臨床試驗相關的試驗活動減少。

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.

我們報告第四季淨收入為 1,430 萬美元，而 2023 年同期為 70 萬美元。全年而言，我們報告淨收入為 1750 萬美元，而 2023 年淨虧損為 2510 萬美元。本季末，我們的現金、現金等價物和短期投資為 7,730 萬美元，高於 2023 年底的 5,690 萬美元。

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 net product sales and $15 million to $18 million of contract revenues from collaborations. 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.

展望 2025 年的財務前景，我們預計總收入約為 2 億至 2.1 億美元，其中包括約 1.85 億至 1.92 億美元的淨產品銷售額和 1500 萬至 1800 萬美元的合作合約收入。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。總而言之，2024 年對 Rigel 來說是收入成長和財務紀律持續改善的一年，我們期待這種勢頭延續到 2025 年及以後。

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

說完這些，我想把電話轉回給勞爾。勞爾？

Thank you, Dean.

謝謝你，迪恩。

Moving on to slide 33. As I've stated on this call, 2024 was a year of significant achievements for Rigel. We reached profitability and cash flow breakeven, while delivering on our corporate strategy to grow our hematology and oncology business.

翻到第 33 張投影片。正如我在這次電話會議上所說，2024 年對 Rigel 來說是取得重大成就的一年。我們實現了獲利和現金流收支平衡，同時實現了發展血液學和腫瘤學業務的公司策略。

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. We plan to initiate the dose expansion phase of the study and provide the updated data at a medical meeting later this year.

展望 2025 年，我們的優先事項很明確：繼續發展我們的商業業務、推進我們的開發計劃、尋找新的管道機會並繼續保持財務紀律。我們預計我們的淨產品銷售額將年增約 30%。我們將繼續專注於推進 R289 治療低風險 MDS 的 1b 期研究，並完成研究的劑量遞增部分。我們計劃啟動研究的劑量擴展階段，並在今年稍後的醫學會議上提供更新的數據。

For olutasidenib, we plan to initiate a new Rigel-sponsored Phase 2 study in recurrent 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.

對於奧魯他尼，我們計劃啟動一項由 Rigel 贊助的針對復發性膠質瘤的新的 2 期研究，並繼續支持我們與 MD Anderson 和 CONNECT 組織的策略合作。即使透過所有這些投資來推進我們現有和新的管道項目，我們預計 2025 年全年仍將實現正淨收入。

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.

翻到第 34 張投影片。我很高興 Rigel 達到了公司歷史上的這個關鍵時刻。我們實施的公司策略使我們達到了這樣的水平：我們的商業銷售水平現在使我們能夠以盈利和可持續的方式發展業務。對於公司來說，這確實是一個令人興奮的時刻。

And with that, I'd like to turn the call over to your questions.

現在，我想把電話轉交給你們來回答問題。

(Operator Instructions) Yigal Nochomovitz, Citi.

（操作員指示）Yigal Nochomovitz，花旗。

I have a few. The first one on the product guidance, I think you said $192 million to $195 million. So using the fourth quarter as a base, I'm just -- 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.

我有幾個。第一個關於產品指導的問題，我想您說的是 1.92 億美元到 1.95 億美元。因此，以第四季度為基礎，我只是——您能否就範圍方面的評論給出更多細節？這似乎有點保守。從第四季來看，季度環比複合年增長率似乎約為 1% 至 2%。這是我的第一個問題。

Yeah. So the net revenue guidance is for $185 million to $192 million. 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 build in Q4, and we've seen this typically.

是的。因此淨收入預期為 1.85 億美元至 1.92 億美元。第四季淨產品銷售額為 4,650 萬美元。正如我們在準備好的評論中所說，這是得益於第四季度的庫存增加，我們通常都看到這種情況。

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.

這佔第四季 4,650 萬美元淨收入的約 450 萬美元。因此，當您將其正常化並開始建立 Q1 到 Q4 時，就會建立我們所描述的收入指引。這意味著淨產品銷售額年增約 30%。

Okay. And then I'm curious on REZLIDHIA, 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.

好的。然後我對 REZLIDHIA 感到好奇，您是否有關於那裡治療持續時間的現場數據？我記得幾年前，有一些非常非常好的數據顯示了這種耐久性的強度。

Yigal, 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. At the end of the day, 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 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.

Yigal，好問題。這是戴夫。今天我們不會分享任何這些內容。但我可以告訴你的是，我們還有很大的發展空間。歸根究底，無論何時推出一款產品，只要我們投入兩年時間，你就會獲得許多後續患者。這些患者不會接受臨床試驗中所見的二線或三線治療那樣的治療持續時間。

And so that's kind of where we are right now. So obviously, we do believe our duration of therapy is a significant driver of 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.

這就是我們現在的狀況。因此，顯然，我們確實相信我們的治療時長是採用的重要驅動力，也是我們前進過程中延續的重要驅動力。這就是為什麼我對我們的成長能力感到樂觀，隨著人們意識的增強，隨著我們讓更多的患者接受治療，隨著我們讓更早的患者接受治療，特別是那些使用過一線維奈克拉的患者，我們認為我們可以延長治療持續時間。

And just one last one, if I might. Do you have any data as to the percent of patients that are on GAVRETO by Rigel versus GAVRETO from the prior commercial sponsor?

如果可以的話，我再問最後一個問題。您是否有關於使用 Rigel 的 GAVRETO 的患者百分比與使用先前商業贊助商的 GAVRETO 的患者百分比的數據？

I don't have specific data, but I could tell you our goal was to transition every single patient that was on GAVRETO over to Rigel label product. 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.

我沒有具體的數據，但我可以告訴你，我們的目標是讓每位使用 GAVRETO 的患者轉而使用 Rigel 標籤產品。我認為，我們的銷售額達到 810 萬美元，需求從第三季到第四季不斷增長，而且我們的運行率高於去年 2800 萬美元的運行率，這些都表明我們實現了這一目標。所以我真的不認為我們因此損失了任何病人。

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 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.

事實上，顯然我認為我們正在增加新患者。目前我們很難區分哪些是使用品牌的新患者，哪些是使用 Rigel 的新患者。我們知道他們都是 Rigel 的新病人。但我們認為，由於需求持續上升，我們正在吸引新的患者來接受品牌治療。

Yeah, that was pretty remarkable achievement, that transition, because you typically see a sale 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.

是的，這種轉變是一個非常了不起的成就，因為你通常會看到產品從一家公司銷售到另一家公司。大概六個月的時間裡，你會看到銷售基數比以前低，而這裡的情況並非如此。因此，我們能夠取得這樣的成績實在是太了不起了，我們對此感到非常高興。

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. I'm actually incredibly impressed.

這也表明，我們的整個團隊、醫療事務、市場准入、銷售組織都真正專注於正確的事情，並讓患者得到治療。所以它確實效果非常好。我的確印象非常深刻。

Kalpit Patel, B. Riley Securities.

卡爾皮特‧帕特爾 (Kalpit Patel)，B. 萊利證券 (Riley Securities)。

Hey, good afternoon and thanks for taking the question. Maybe, I want to start first with the TAVALISSE 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?

嘿，下午好，感謝您回答這個問題。也許，我想先從 TAVALISSE 的銷售額開始，看看第四季相對於第三季的成長情況。也許可以評論一下其中有多少是有機銷售成長，有多少是可能發生的價格上漲？

I'm sorry, can you repeat the last part of your question, Kalpit? You said volume versus pricing.

抱歉，卡爾皮特，你能重複一下你問題的最後一部分嗎？您說的是數量與價格。

Yeah, exactly. Just -- was this accounted for by any price increases?

是的，確實如此。只是——這是由價格上漲造成的嗎？

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's bottles shipped to patients and clinics. As a matter of fact, it was the ninth consecutive quarterly high that we've hit.

是的，我們在第四季沒有任何價格上漲，所以這都是銷量上漲。我想說的是，我們運送給病人和診所的瓶子的需求達到了有史以來的最高水平。事實上，這是我們連續第九個季度創下新高。

We also had a higher percentage of new patient 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 build, which is typical in the last quarter of the year. But demand definitely increased from Q3 to Q4 as the new patient starts.

我們第四季度的新患者數量（或新患者與現有患者的比例）也有所增加，這推動了新患者的增加。因此，正如迪恩所說，我們也得到了一些庫存增加的幫助，這在去年最後一個季度很常見。但隨著新病人的到來，從第三季到第四季度，需求肯定有所增加。

And we did in our press release highlight the unit volume, the demand volume, as Dave suggested, the demand or the bottles shipped to patients and clinics, that's really the key to the business. Those are the bottles that are going to go to patients.

正如戴夫所說，我們在新聞稿中確實強調了單位數量、需求量、運送給患者和診所的瓶子的需求，這才是業務的關鍵。這些瓶子是要送給病人的。

Incrementally, there's the bottles left in the distribution channels that we report, and those are inventory levels. For TAVALISSE, that inventory level benefit for Q4 was about $3 million, and that's in the $4.5 million I described. Again, TAVALISSE was benefited by about $3 million. That said, again, the demand is consistently growing, and that's the important measure of the business.

我們報告的分銷管道中剩餘的瓶子數量逐漸增多，這些就是庫存水準。對於 TAVALISSE 來說，第四季的庫存水準收益約為 300 萬美元，而這正是我所描述的 450 萬美元。TAVALISSE 再次獲利約 300 萬美元。話雖如此，但需求仍在持續成長，這是衡量業務的重要指標。

Okay. Okay, great. 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. Are you going to do a head-to-head study against vorasidenib or are you trying to maybe position your drug for a different grade glioma, maybe a higher grade, Grade 3 or 4?

好的。好的，太好了。然後也許轉換到你的神經膠質瘤項目，即計劃中的研究。我知道你還在那裡進行設計工作。但我對這裡的策略很好奇。您是否打算對 Vorasidenib 進行頭對頭研究，或者您是否試圖將您的藥物定位於不同級別的膠質瘤，也許是更高級別的，3 級或 4 級？

Lisa?

麗莎？

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 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.

是的。謝謝你的提問。我認為現在評論這項研究的設計還為時過早。我們剛開始我們的 KOL 討論和廣告板並正在製定該計劃，但我們很樂意在今年晚些時候向您提供更多有關此方面的信息。

So for both 289 and olut and glioma, our plan is to later this year as we have some discussions with regulatory agencies to settle on what the plan is exactly. We'll come back to you and share that with you. But it probably will be in the second half of the year.

因此，對於 289、olut 和神經膠質瘤，我們的計劃是在今年晚些時候，因為我們與監管機構進行了一些討論，以確定具體的計劃。我們會回來和你們分享。但很可能要等到今年下半年。

Joe Pantginis, H.C. Wainwright.

喬·潘吉尼斯（H.C.）溫賴特。

Hi, everybody good afternoon and thanks for taking my question. So my first question is a two-parter for TAVALISSE, if you don't mind. So in the US, 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 one to two years ago? That's part one.

大家下午好，感謝您回答我的問題。如果您不介意的話，我的第一個問題是向 TAVALISSE 提出兩個問題。那麼我想，在美國，您會如何描述——嗯，首先，您能描述一下差異或續藥的百分比以及新處方的增長嗎？與一兩年前相比，您現在採取了哪些措施來幫助增加新處方？這是第一部分。

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 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, as a matter of fact, the highest percentage we've ever seen. And so clearly, I think adoption is growing.

是的。所以我認為——喬，這個問題問得很好。我認為，正如我之前所說，我們在第四季度注意到的一個非常好的情況是，我們的患者（即接受治療的患者總數）的比例有所增加，其中包括前幾個季度的延續性患者以及新患者。更高比例的病例是由新患者引起的，事實上，這是我們見過的最高比例。顯然，我認為採用率正在成長。

I think some of the things that we're doing now that we've learned over the past is certainly 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.

我認為我們現在所做的一些事情是我們過去學到的，肯定是針對臨床醫生的，我們花了大量的時間和精力來確保我們正在做的事情。透過不同的管道擴大覆蓋範圍是我們正在做的另一件事。

And then I think the last part is community practices play a big role in the management of ITP. And I think we target the specific GPOs out there among the community practices to ensure that they're aware of our -- of ITPs unique value proposition -- that unique value proposition in ITP, sorry.

我認為最後一部分是社區實踐在 ITP 管理中發揮重要作用。我認為我們針對社區實踐中的特定 GPO，以確保他們了解我們 — — ITP 的獨特價值主張 — — ITP 中的獨特價值主張，抱歉。

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 ex-US opportunities as you expand geographically. Are there any components that are unique to ex US? Like you said, community centers, for example, how is the drug delivered there? Are there differences in the initial lines of therapy? Any particular components you can point to ex US that might differ from the US?

當然不是。所以 — — 我想，第二部分會包含您剛才討論的一些內容。我想討論一下你們在地理上擴張時在美國以外的機會。是否存在美國以外獨有的組件？就像你說的，例如社區中心，藥物是如何送到那裡的？初始治療方法有差異嗎？您能指出美國以外的哪些特定組件可能與美國不同嗎？

I think the best thing for me to do is kind of talk about how the US may be unique in that its use of TPOs particularly Nplate is probably more driven by that community practice kind of buy-and-bill sort of mentality. And I think particularly, in Japan, some of the differences there that they've seen is a more -- 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.

我認為對我來說最好的事情是談論美國的獨特之處，因為它對 TPO 特別是 Nplate 的使用可能更多地受到社區實踐的買單心態的驅動。我認為，特別是在日本，他們看到的一些差異是人們更願意使用聯合療法。因此我認為，全球各地的患者治療方式和臨床醫生對 ITP 的管理方式存在一些差異。

But like I said, here in the US, it's a lot. It's treated. It's not a disease. It's a benign hematologic condition where if a hematologist, oncologist sees this, they're not going to refer it. They're going to treat it. So I think we have a very kind of diffused model here in the US, which I think might be a little more concentrated in other countries outside the US.

但就像我說的，在美國，這種情況很多。已治療。這不是一種疾病。這是一種良性血液疾病，如果血液學家、腫瘤學家發現這種情況，他們不會將其轉診。他們會對其進行治療。所以我認為我們在美國有一個非常分散的模式，而在美國以外的其他國家可能會更加集中一些。

No, that's helpful. I appreciate that color. 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 rightsized? And as you look to add assets and are in early launch stages, what would you envision as potential growth of the size of your sales force?

不，這很有幫助。我很欣賞那個顏色。如果您不介意的話，我的最後一個問題更多的是關於基礎設施的問題。那麼截至目前，您是否認為您的銷售團隊規模合適？當您尋求增加資產並處於早期啟動階段時，您認為銷售團隊規模的潛在成長是多少？

Yeah, great question, Joe. I would say that what we've done with REZLIDHIA and GAVRETO 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 and business operations. So we have tremendous synergies there.

是的，喬，這個問題問得很好。我想說，我們與 REZLIDHIA 和 GAVRETO 合作所做的就是確保我們具有協同效應。而且不僅僅是銷售，對吧？它涉及整個品牌團隊。它涉及市場准入，這是當今產品商業化的重要組成部分，也是我們的營運和分析能力以及業務運營的重要組成部分。因此，我們在這方面具有巨大的協同效應。

But I'll just say that we're constantly looking at our impactable market and who -- how many customers we need to call on to ensure that we create impact, positive impact on our brands in the market. And depending on the product we bring on board, 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 or then I think we have the capacity to cover. But if it's something that's in a subspecialty that might -- that we're maybe not calling on today, then obviously, we'd need to address that.

但我只想說，我們一直在關注我們的可影響市場以及我們需要拜訪多少客戶，以確保我們在市場上對我們的品牌產生影響、積極影響。根據我們引入的產品和可能涉及的專科醫生的不同，我們是否需要建立銷售支援可能會有所不同。如果它主要用於社區，那麼我認為我們有能力覆蓋。但如果這是屬於專科領域的事情——我們今天可能不會打電話詢問，那麼顯然，我們需要解決這個問題。

But it's part of the assessment of each of those individual opportunities as we decide to bring them in or not.

但當我們決定是否引入這些機會時，這是我們對每個單獨機會進行評估的一部分。

Kristen Kluska, Cantor.

克里斯汀·克魯斯卡（Kristen Kluska），領唱。

This is [Ian] on Kristen's line. Could you talk a bit about your plan to initiate the expansion phase of the Phase I study of R289 this year? Any color you can provide here, particularly when you plan to start and how you'll go about choosing the doses?

我是 Kristen 的接線生 [Ian]。能否談談今年啟動 R289 第一階段研究擴展階段的計畫？您可以提供任何顏色嗎，特別是您計劃何時開始以及如何選擇劑量？

Yeah. Thanks for the question. As you know, as I mentioned, we're currently enrolling in dose level 6 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 safety and activity.

是的。謝謝你的提問。正如我所提到的，您知道，我們目前正在招募劑量等級 6 的劑量遞增患者。因此，我們要做的第一件事就是完成該劑量水平的招募，並觀察其安全性和活性。

Dose selection for expansion will be based on the typical things like safety, PK, PD, a little bit of activity -- 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 of a dose to carry forward into -- for further clinical evaluation.

擴展劑量的選擇將基於典型因素，例如安全性、PK、PD、少量活性——正如您在幻燈片上看到的——您可能已經在幻燈片上註意到，我們計劃每組招募最多 20 名患者，因為我們確實希望對劑量進行穩健的確定，以便進行進一步的臨床評估。

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 what's going on in dose escalation in this last cohort.

正如我們所提到的，我們期待今年晚些時候開業。正如我所提到的，確切的時間實際上取決於最後一批患者的劑量增加。

(Operator Instructions) Farzin Haque, Jefferies.

（操作員指示）Farzin Haque，Jefferies。

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 ASH update in the second half? And then I have a follow-up.

也涉及 R289 低風險 MDS 計劃。所以我想問一下，對於正在進行的分劑量進一步劑量評估，您是如何設定預期的？然後是數據更新的時間，下半年是否會有更多 ASH 更新？然後我有一個後續問題。

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 more or less continuous suppression of inflammation as opposed to kind of an on-off, on-off. So we're really looking forward to seeing the data from the BID dose levels.

是的。正如您在我們的文章中註意到的——感謝您的提問，非常有趣。正如您所注意到的，在劑量遞增階段，我們將 [TAC] 的給藥方式從每日一次改為每日兩次，因為我們認為從生物學角度來看，或多或少持續抑制發炎比斷斷續續地抑制更有意義。因此，我們非常期待看到 BID 劑量水平的數據。

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.

與預期的數據呈現時間相關，我認為我們最好的機會是 ASH。因此，我們期待有機會展示更新的研究數據。

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 is working, its efficacy, importantly its safety. So that does take some time to do that. So by necessity has to be towards the end of this calendar year.

請記住，我們希望對每位患者進行四到六個月的接觸，以便正確評估產品是否有效、是否有效，更重要的是是否安全。所以這確實需要一些時間。因此必然會在今年底前完成。

Got it. That makes sense. And then we'll be waiting for the mature dose escalation data prior to meeting with the regulators for a registrational path?

知道了。這很有道理。然後，我們將等待成熟的劑量遞增數據，然後再與監管機構會面確定註冊途徑？

I think we'll give some more information on that later as the data mature more.

我認為隨著數據更加成熟，我們稍後會提供更多相關資訊。

But we won't wait until 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.

但我們不會等到年底才與他們互動。快速通道指定的好處是，它允許他們和我們更緊密地合作。這真的很有幫助。

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

目前沒有其他問題。我想把發言權交還給勞爾·羅德里格斯先生，請他作最後評論。

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.

好的，謝謝你。我要感謝你們今天參加這次電話會議，感謝你們提出的好問題，特別是感謝你們對 Rigel 的持續關注。對我們來說，這確實是具有里程碑意義的一年。我們為 2024 年所取得的成就感到無比自豪，並對 2025 年充滿期待。我們面臨著一些重要的事情，我認為我們完全有能力成功地完成它們。

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, I look forward to updating you on future calls, and have a great day.

在我們離開之前，我想感謝我們的員工一直致力於改善患者的生活，並使 2024 年成為我們如此成功的一年。因此，我期待在未來的通話中向您通報最新情況，並祝您有美好的一天。

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。現在您可以斷開線路。感謝您的參與。