Rigel Pharmaceuticals Inc (RIGL) 2025 Q1 法說會逐字稿

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

問候並歡迎參加 Rigel Pharmaceuticals 2025 年第一季財務電話會議。（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 first-quarter 2025 financial results and business update conference call. The financial press release for the first-quarter 2025 was issued a short while ago and can be viewed along with the slides for this presentation in the News and Events section of our Investor Relations site on rigel.com.

歡迎參加我們的 2025 年第一季財務業績和業務更新電話會議。2025 年第一季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」部分中與本簡報的幻燈片一起查看。

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.

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。

The description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 2024, and subsequent filings with the SEC. Including our quarter-one quarterly report on Form 10-Q on file with the SEC. Any forward-looking statements are made only as of today's date, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances.

這些風險的描述可以在我們最新的截至 2024 年 12 月 31 日的 10-K 表格年度報告以及隨後向美國證券交易委員會提交的文件中找到。包括我們向美國證券交易委員會提交的 10-Q 表第一季季度報告。任何前瞻性陳述僅截至今日為止，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 would 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勞爾·羅德里格斯。勞爾。

Thank you, Ray, and thank you, everyone, for joining today. Also with us today are Dave Santos, our Chief Commercial Officer; Lisa Rojkjaer, our Chief Medical Officer; and Dean Schorno, our Chief Financial Officer.

謝謝你，雷，也謝謝大家今天的到來。今天與我們一起出席的還有我們的商務長 Dave Santos、我們的醫療長 Lisa Rojkjaer 和我們的財務長 Dean Schorno。

I'll begin on slide 4, we will provide an overview of Rigel's business and our results for the first quarter of 2025. I want to start the call today by highlighting our strong start to the year. Today, for the first quarter of 2025, we reported year-over-year net product sales growth of 68% from our expanding commercial portfolio. In addition, we increased collaboration revenue from our ex-US marketing partners.

我將從第 4 張投影片開始，概述 Rigel 的業務和 2025 年第一季的業績。今天，我想先強調我們今年的強勁開局。今天，我們報告稱，2025 年第一季度，我們不斷擴大的商業產品組合的淨產品銷售額同比增長 68%。此外，我們也增加了來自美國以外行銷合作夥伴的合作收入。

With total revenue of $53.3 million for the quarter, and continued financial discipline, we were able to generate $11.4 million in net income this quarter. Now, this is a time when the general business environment is challenging, especially for the biotech market, but highlights the robustness of our corporate strategy and consequently, our unique position. Rigel is a growing, profitable company with important clinical opportunities at hand that we are able to fund ourselves.

本季總收入為 5,330 萬美元，在繼續嚴格財務紀律的前提下，我們本季實現了 1,140 萬美元的淨收入。現在，整體商業環境充滿挑戰，尤其是對於生技市場而言，但這凸顯了我們企業策略的穩健性，以及我們獨特的地位。Rigel 是一家成長型、獲利型公司，擁有重要的臨床機會，我們能夠自行籌資。

On this call, the team will provide you with greater details on our position and this quarter's results. They will provide an overview update on the strength of our growing commercial business that now includes three commercial products after the acquisition of our latest product, GAVRETO.

在本次電話會議上，團隊將向您提供有關我們的立場和本季業績的更多詳細資訊。他們將概述我們不斷成長的商業業務的實力，在收購我們的最新產品 GAVRETO 後，該業務現在包括三種商業產品。

Lisa will provide updates on the advancement of our development pipeline, including R289, our novel and selective dual IRAK1/4 inhibitor. R289 is currently being evaluated in a Phase 1B clinical study in patients with relapse or refractory lower risk MDS. She will also highlight our plans to expand olutasidenib with the planned initiation of a Phase 2 study in recurrent glioma. Beyond these Rigel-led development programs, we also remain committed to evaluating new opportunities to expand our hematology and oncology portfolio through business development, as we did with REZLIDHIA and GAVRETO.

Lisa 將介紹我們開發流程的最新進展，包括 R289（我們的新型選擇性雙 IRAK1/4 抑制劑）。R289 目前正在針對復發或難治性低風險 MDS 患者進行 1B 期臨床研究評估。她還將重點介紹我們擴大奧魯他尼治療範圍的計劃，並計劃啟動復發性膠質瘤的 2 期研究。除了這些由 Rigel 主導的發展計劃之外，我們還將繼續致力於評估透過業務發展擴大我們的血液學和腫瘤學產品組合的新機會，就像我們對 REZLIDHIA 和 GAVRETO 所做的那樣。

In 2025, we will continue to focus on commercial growth while maintaining that financial discipline that has contributed to the results today and updates today. We continue to anticipate 2025 total revenue of $200 million to $210 million and to report positive net income for the full-year 2025, while advancing and expanding our development pipeline. This is a testament to the strength of our business and the execution of our corporate strategy to grow our hematology and oncology business.

2025 年，我們將繼續專注於商業成長，同時保持對今天的結果和更新做出貢獻的財務紀律。我們繼續預計 2025 年總收入將達到 2 億至 2.1 億美元，並預計 2025 年全年淨收入將為正，同時推進和擴大我們的開發管道。這證明了我們業務的實力以及我們發展血液學和腫瘤學業務的公司策略的執行。

Now, before I turn the call over to Dave, I want to take a moment to discuss our RIPK1 Inhibitor Program that is partnered with Lilly. Last week, we notified Lilly that we will not exercise our right to share in future development expenses for ocadusertib, known previously as Rigel's R552. This incremental development cost share, which we believe could be substantial and near term, could have resulted in slightly higher royalty rates for Rigel on future net sales.

現在，在我將電話轉給戴夫之前，我想花點時間討論一下我們與禮來公司合作的 RIPK1 抑制劑計劃。上週，我們通知禮來公司，我們將不會行使分享 ocadusertib（之前稱為 Rigel 的 R552）未來開發費用的權利。我們認為，這項增量開發成本份額在短期內可能相當可觀，可能會導致 Rigel 未來淨銷售額的專利費率略有提高。

While we continue to be very excited about the potential of ocadusertib, we have concluded that it is optimal for us to invest our own and our own internal pipeline assets such as R289 and olutasidenib. Dean will tell you a bit more about the financial impact of this in his remarks.

雖然我們仍然對 ocadusertib 的潛力感到非常興奮，但我們得出的結論是，投資我們自己和我們自己的內部管道資產（例如 R289 和 olutasidenib）是最佳選擇。迪恩將在演講中進一步介紹此事的財務影響。

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

現在，我將把電話轉給戴夫，讓他提供商業更新。戴夫。

Thank you, Raul. On slide 6, you'll see our three commercial products, TAVALISSE, GAVRETO, and REZLIDHIA. Then to slide 7, we are pleased with the strong year-over-year growth in revenues in the first quarter of 2025. You can see how our quarterly and annual sales have increased since 2021 in the chart.

謝謝你，勞爾。在第 6 張投影片上，您將看到我們的三種商業產品：TAVALISSE、GAVRETO 和 REZLIDHIA。然後到第 7 張投影片，我們對 2025 年第一季營收的強勁年成長感到滿意。您可以在圖表中看到自 2021 年以來我們的季度和年度銷售額是如何成長的。

We have grown each quarter's sales over the previous year, and that growth continues. In the first quarter of 2024, we reported $26 million and now for the first quarter of 2025, we generated $43.6 million representing a 68% increase. Our year-over-year growth was driven by the addition of GAVRETO to our portfolio last year, as well as growth in both TAVALISSE and REZLIDHIA.

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。2024 年第一季度，我們的營收為 2,600 萬美元，而 2025 年第一季度，我們的營收為 4,360 萬美元，成長了 68%。我們的年成長得益於去年 GAVRETO 加入我們的產品組合，以及 TAVALISSE 和 REZLIDHIA 的成長。

Our commercial team has been dedicated to execution, driving continued momentum for TAVALISSE, raising awareness for GAVRETO after a successful transition into our portfolio, and improving both institutional and community demand for REZLIDHIA. My sincere thanks to the entire team for all their hard work.

我們的商業團隊一直致力於執行，推動 TAVALISSE 的持續發展，在成功轉型到我們的投資組合後提高 GAVRETO 的知名度，並提高機構和社區對 REZLIDHIA 的需求。我衷心感謝整個團隊的辛勤工作。

Slide 8 shows a summary of our commercial performance by product. First, on TAVALISSE. I'm pleased to report another strong quarter in which we generated $28.5 million in net product sales, an increase of 35% compared to the first quarter of 2024. This growth was driven by a continued strong patient demand, with another consecutive quarterly record high.

投影片 8 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，本季我們又取得了強勁的業績，淨產品銷售額達到 2,850 萬美元，與 2024 年第一季相比成長了 35%。這一成長是由持續強勁的患者需求推動的，連續一個季度創下歷史新高。

For GAVRETO, we delivered $9 million in net product sales in Q1. As a reminder, GAVRETO became commercially available from Rigel in late June 2024. And lastly, for REZLIDHIA, we reported $6.1 million in net product sales, an increase of 25% compared to the prior year period.

對於 GAVRETO，我們在第一季實現了 900 萬美元的淨產品銷售額。提醒一下，GAVRETO 將於 2024 年 6 月下旬由 Rigel 上市。最後，對於 REZLIDHIA，我們報告其淨產品銷售額為 610 萬美元，比去年同期成長了 25%。

Moving to slide 9, I'll provide more color on our commercial performance. TAVALISSE continues to grow steadily as the foundation of our portfolio, consistently hitting new record quarterly highs in patient demand. That steady growth has been driven by new patients starting on TAVALISSE each quarter and the subsequent increased carryover that it's generated. We expect this trend to continue throughout 2025. In addition, in the first quarter, we completed a successful streamlining of our distribution network to improve efficiency and be consistent across the entire portfolio.

轉到幻燈片 9，我將提供有關我們商業表現的更多細節。TAVALISSE 作為我們產品組合的基礎，持續穩定成長，病患需求​​不斷創下季度新高。這種穩定的成長是由每季開始使用 TAVALISSE 的新患者以及隨後產生的增加的結轉所推動的。我們預計這一趨勢將持續到 2025 年。此外，在第一季度，我們成功完成了分銷網絡的精簡，以提高效率並保持整個產品組合的一致性。

GAVRETO continued to grow nicely under our ownership. In the first quarter of 2025, the third full quarter of GAVRETO being in the portfolio, we generated $9 million in revenue, approximately 15% year-over-year growth compared to the first quarter of 2024 as reported by the previous owner of the product. On a sequential basis, we saw 11% revenue growth versus Q4 of 2024, driven by additional carryover from existing patients as well as new patients.

在我們的領導下，GAVRETO 繼續順利發展。2025 年第一季度，即 GAVRETO 加入投資組合後的第三個完整季度，我們創造了 900 萬美元的收入，與產品前所有者報告的 2024 年第一季度相比，同比增長約 15%。與 2024 年第四季相比，我們的營收季增了 11%，這得益於現有患者和新患者的額外結轉。

The seamless transition into our portfolio has provided a solid platform for growth that we will continue to build on. We are confident we can continue to grow GAVRETO as we begin more targeted efforts on expanding our base of prescribers, particularly since the use of RET inhibitors in non-small cell lung cancer should continue to expand in the frontline setting, consistent with the updated guidelines I discussed last quarter. Overall, we believe that RET inhibitor use will continue to grow beyond 2025 and GAVRETO will grow in turn.

無縫過渡到我們的投資組合為我們將繼續發展提供了堅實的成長平台。我們相信，隨著我們開始更有針對性地努力擴大我們的處方醫生基礎，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中的使用應該在前線環境中繼續擴大，這與我上個季度討論的最新指南一致。總體而言，我們相信 RET 抑制劑的使用將在 2025 年後繼續增長，而 GAVRETO 也將隨之增長。

For REZLIDHIA, we continue to drive new patient starts as we raise awareness for the product, and especially as clinicians become more aware of REZLIDHIA's efficacy in post-venetoclax patients. They believe that activity is clinically meaningful, as these patients are very difficult to treat with other therapies.

對於 REZLIDHIA，隨著我們提高該產品的知名度，特別是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，我們將繼續推動新患者的開始治療。他們認為這項活動具有臨床意義，因為這些患者很難用其他療法治療。

We are also focused on educating healthcare professionals on the benefits of patients remaining on therapy, consistent with data that was presented at the ASH meeting in December. The analysis showed that while some patients with mutant IDH1 relapse or refractory AML achieved responses very quickly, sometimes within one to two months of treatment. Other patients who continue treatment with REZLIDHIA require up to six months to achieve CR/CRH and even up to 10 months for an overall response.

我們也致力於教育醫療保健專業人員了解患者繼續接受治療的益處，這與 12 月 ASH 會議上提供的數據一致。分析表明，雖然一些突變IDH1復發或難治性AML患者很快便獲得了反應，有時在治療後一到兩個月內即可獲得反應。其他繼續使用 REZLIDHIA 治療的患者需要長達六個月才能達到 CR/CRH，甚至需要長達 10 個月才能獲得整體反應。

This data supports the prescribing information that suggests treating patients for at least six months to allow time for clinical response in patients without disease progression or unacceptable toxicities. We believe we still have a significant opportunity to grow as REZLIDHIA's use in mutant IDH1 relapse to refractory, acute myeloid leukemia, and we are focused on building on the scientific data currently available in this important population of AML patients.

這些數據支持處方訊息，建議對患者進行至少六個月的治療，以便患者有時間在沒有病情進展或不可接受的毒性的情況下出現臨床反應。我們相信，隨著 REZLIDHIA 在突變 IDH1 復發至難治性急性髓系白血病中的應用，我們仍然有很大的發展機會，並且我們專注於在這一重要的 AML 患者群體中現有的科學數據的基礎上進行構建。

Finally, moving to slide 10, we continue to work on expanding access to our products 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. In addition, our partners continue to pursue regulatory approvals for TAVALISSE in new markets. Late last year, Knight Therapeutics announced it had received regulatory approval for TAVALISSE in Mexico. And in January, Kissei announced regulatory approval for TAVALISSE in the Republic of Korea.

最後，翻到第 10 張投影片，我們持續致力於擴大我們產品在美國以外市場的覆蓋範圍。TAVALISSE 在日本有售，在歐洲以 TAVLESSE 品牌銷售，並透過我們的合作夥伴 Kissei、Grifols 和 Medison 在加拿大和以色列銷售。此外，我們的合作夥伴繼續尋求 TAVALISSE 在新市場的監管批准。去年年底，Knight Therapeutics 宣布已獲得墨西哥監管部門對 TAVALISSE 的批准。今年 1 月，Kissei 宣布 TAVALISSE 已獲得韓國監管部門批准。

For REZLIDHIA, in 2024, we expanded our relationship with Kissei to include Japan, the Republic of Korea, and Taiwan 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, 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 partner -- our products to other patients and markets around the globe.

對於 REZLIDHIA，2024 年，我們擴大了與 Kissei 的關係，將所有潛在適應症涵蓋在日本、韓國和台灣，並且我們與 Dr. Reddy's 簽訂了獨家許可協議，涵蓋 Dr. Reddy's 整個地區（包括拉丁美洲和其他地區）的所有潛在適應症。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夥伴關係的其他機會，以便將我們的合作夥伴——我們的產品帶給全球其他患者和市場。

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. I will now provide an overview of our pipeline progress and plans for the remainder of the year.

謝謝，戴夫。我現在將概述我們的管道進展和今年剩餘時間的計劃。

I'm on slide 12. From our development pipeline, we're particularly excited by the progress in the clinical development of R289, our novel dual IRAK1 and IRAK4 inhibitor in lower risk myelodysplastic syndrome, or MDS, and olutasidenib in mutant IDH1 recurrent glioma. Beginning with R289, our Phase 1b study in patients with relapse refractory lower risk of MDS is progressing well, and we're currently enrolling dose level six. We look forward to providing updated data from this study in the second half of this year.

我在第 12 張投影片。從我們的開發流程來看，我們對 R289 臨床開發的進展感到特別興奮，R289 是我們用於治療低風險骨髓增生異常綜合徵 (MDS) 的新型雙重 IRAK1 和 IRAK4 抑製劑，而奧魯他尼則用於治療突變型 IDH1 復發性膠質瘤。從 R289 開始，我們針對復發難治性低風險 MDS 患者進行的 1b 期研究進展順利，目前正在招募六級劑量的患者。我們期待在今年下半年提供這項研究的最新數據。

From a regulatory perspective, the granting of both fast track designation for the treatment of patients was previously treated transfusion dependent lower risk MDS, and orphan drug designation for MDS is an acknowledgement by the FDA of both the unmet medical need of the lower risk MDS patient population and the potential of R289.

從監管角度來看，授予用於治療先前接受輸血依賴治療的低風險MDS 患者的快速通道資格和用於治療MDS 的孤兒藥資格表明 FDA 對低風險 MDS 患者群體未滿足的醫療需求和 R289 的潛力的認可。

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 and recurrent glioma later this year.

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 Cancer Consortium 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 突變引起的癌症中具有潛力，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。我們預計今年稍後啟動一項由 Rigel 贊助的 2 期研究，以評估奧魯他尼和復發性膠質瘤。

In addition, all four clinical trials under our MD Anderson collaboration are now open for enrollment, as is the CONNECT’s TarGeT study evaluating the combination of the olutasidenib with temozolomide as maintenance therapy in adolescence and young adults with IDH1-mutated high-grade glioma. Consistent with our strategy and evidenced by our acquisitions of olutasidenib and pralsetinib, we remain focused on evaluating potential opportunities to expand our portfolio by in-licensing or acquiring products that would be a strategic fit for our hematology and oncology focus.

此外，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，CONNECT 的 TarGeT 研究也已開放招募，該研究評估了奧魯他尼與替莫唑胺聯合用於治療青少年和年輕成人 IDH1 突變高級別膠質瘤的維持治療。與我們的策略一致，透過收購 olutasidenib 和 pralsetinib 可以看出，我們將繼續專注於評估透過授權或收購符合我們血液學和腫瘤學重點策略的產品來擴大我們產品組合的潛在機會。

Now we'll spend a few moments on our R289 program. I'm now on slide 14, which presents an overview of the value proposition of R289 and lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the US. With recent development efforts and lower-risk MDS focusing primarily on first-line therapies, there's a high unmet need for next-line therapies, particularly for previously treated transfusion-dependent patients.

現在我們將花一些時間討論我們的 R289 程序。我現在看到第 14 張投影片，它概述了 R289 和低風險 MDS 的價值主張。美國約有 12,000 名接受過治療的低風險 MDS 患者。由於最近的開發努力和低風險 MDS 主要集中在一線療法上，因此對下一線療法的需求很高，特別是對於先前接受過輸血治療的患者。

This regulation of inflammatory signaling is key to the pathogenesis of lower-risk MDS, and IRAK 1 and 4 mediate this process. Blocking both IRAK 1 and 4 may suppress marrow inflammation and leukemic stem and progenitor cell function and restore hematopoeisis. R835, the active moiety of R289, blocks toll-like receptor and IL-1 receptor signaling in vitro and was active in various preclinical models of inflammation. Clinical proof of concept of this anti-inflammatory effect came from a healthy volunteer study in which R835 markedly suppressed LPS-induced cytokine release compared to placebo. As a reminder, R289, which is being currently evaluated in the clinic, is the oral pro-drug that is rapidly converted to R835 in the gut.

這種發炎訊號的調節是低風險 MDS 發病機制的關鍵，而 IRAK 1 和 4 則介導此過程。阻斷 IRAK 1 和 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。提醒一下，目前正在臨床評估的 R289 是一種口服前藥，可在腸道中快速轉化為 R835。

As I mentioned, 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.

正如我所提到的，R289 同時擁有 FDA 快速通道和孤兒藥資格，這使得該分子擁有快速監管途徑、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 demonstrated promising preliminary safety and clinical activity in elderly, heavily pre-treated patients with relapsed or refractory lower-risk MDS.

此外，R289 迄今在 1b 期研究中表現出良好的初步臨床特性。最近在 ASH 年會上公佈的初始劑量遞增數據顯示，對於復發或難治性低風險 MDS 的老年、接受過大量預先治療的患者，該藥物具有良好的初步安全性和臨床活性。

On slide 15, we outlined 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 15 張投影片上，我們概述了低風險 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, patients are eligible, and luspatercept. A imetelstat was also approved last year for ESA failure, high transfusion burden, lower-risk MDS. With eight-week transfusion independence rates approaching 40% with luspatercept and a imetelstat, many patients require an alternative treatment option.

除了輸血之外，初始治療還包括紅血球生成刺激劑（ESA）（患者符合條件）和luspatercept。imetelstat 去年也獲得批准用於治療 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。

Although hypomethylating agents or HMAs are approved, the percentage of patients achieving transfusion independence is low. Therefore, there's a high unmet need for safe, effective treatment options following failure of approved therapies, particularly for previously treated transfusion dependent patients.

儘管低甲基化劑或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輸血治療的患者。

On slide 16, you'll see the design of our ongoing open label dose escalation, dose expansion Phase 1b study, and relapsed refractory lower-risk MDS patients with either symptomatic anemia or transfusion dependence. Primary endpoints are safety and selection of the recommended Phase 2 dose, and secondary endpoints include transfusion independence, hematologic improvement, response rates, and PK. Enrollment is ongoing into dose level six and the dose escalation part of the study, evaluating a dose of 500 mg twice daily.

在第 16 張投影片上，您將看到我們正在進行的開放標籤劑量遞增、劑量擴展 1b 期研究的設計，以及患有症狀性貧血或輸血依賴的複發難治性低風險 MDS 患者。主要終點是安全性和選擇建議的 2 期劑量，次要終點包括輸血獨立性、血液學改善、反應率和 PK。研究的劑量等級六和劑量遞增部分正在進行招募，評估劑量為每天兩次，每次 500 毫克。

Once enrollment of this cohort is complete, the plan is to select two doses to be compared head-to-head in the dose expansion part of the study to optimize selection of the recommended Phase 2 dose for further evaluation. In addition, once the recommended Phase 2 dose has been determined, an exploratory cohort of first-line lower risk MDS patients will be opened to evaluate R289 at that dose in an earlier line of therapy. Initial data from the study was presented at ASH in late 2024.

一旦完成此隊列的招募，計劃選擇兩種劑量在研究的劑量擴展部分進行頭對頭比較，以優化選擇建議的 2 期劑量以供進一步評估。此外，一旦確定了建議的 2 期劑量，將開放一線低風險 MDS 患者的探索性隊列，以評估該劑量的 R289 在早期治療中的療效。該研究的初步數據於 2024 年底在 ASH 上公佈。

On slide 17, you'll see the initial safety data that was presented. To put the safety data into context, this was an elderly, heavily pre-treated patient population with a median age of 76, more than 70% of whom had received either luspatercept or an HMA. Almost three quarters had a high transfusion burden, meaning they frequently received red cell transfusions before they enrolled in the study.

在第 17 張投影片上，您將看到所呈現的初始安全資料。將安全數據放在背景中，這是一群年長的、接受過大量預先治療的患者，平均年齡為 76 歲，其中 70% 以上接受過 luspatercept 或 HMA 治療。近四分之三的受試者輸血負擔很重，這意味著他們在參與研究之前就經常接受紅血球輸血。

In this population, R289 was generally well tolerated, with low-grade nausea, diarrhea, fatigue, chills, and pruritus being most frequently reported overall. Nausea and diarrhea were also two of the most frequently reported related adverse events that are indicated in the table on the slide. Overall, the most frequently reported grade 3 or four adverse events were anemia, decreased platelet count, pneumonia, and increased ALT, occurring in only two patients each. So thus far, what we're not seeing is a high incidence of cytopenias and infections, which is encouraging.

在該族群中，R289 通常耐受性良好，整體而言最常見的症狀是輕度噁心、腹瀉、疲勞、發冷和搔癢。噁心和腹瀉也是幻燈片表格中列出的兩種最常見的相關不良事件。總體而言，最常報告的 3 級或 4 級不良事件是貧血、血小板計數減少、肺炎和 ALT 升高，每種患者僅發生在兩名患者身上。因此到目前為止，我們還沒有看到血球減少症和感染的高發生率，這是令人鼓舞的。

On slide 18, we show the preliminary of efficacy data. The swimmer plot shows each patient and the red cell transfusions by dose group, starting with the lowest dose group, 250 mg daily, on top. For the IWG 2018 criteria, the transfusion history for each patient was collected for 16 weeks prior to R289 administration to establish the baseline transfusion frequency for each patient shown to the left of day zero, which is indicated by the red arrow. 18 patients were valuable for efficacy, meaning that they had received one or more R289 doses and had at least one efficacy assessment.

在投影片 18 上，我們展示了初步的功效數據。游泳圖按劑量組顯示了每位患者和紅血球輸注情況，從最低劑量組（每天 250 毫克）開始。對於 IWG 2018 標準，在 R289 給藥前 16 週收集了每位患者的輸血史，以確定每位患者的基線輸血頻率，如第零天左側所示，以紅色箭頭所示。 18 名患者對療效有價值，這意味著他們已經接受了一劑或多劑 R289 並至少進行過一次療效評估。

Red blood cell transfusion independence, lasting eight weeks or longer, was achieved by three patients, one receiving 500 mg daily and two receiving 750 mg daily. Red blood cell transfusion independence lasted for more than six months in two patients, and one patient also achieved a narrow complete response. The median duration of transfusion independence was 29 weeks. In addition, one high transfusion burden patient receiving 500 mg daily achieved a minor HI-E response with a 64% reduction in red cell transfusions compared to baseline.

三名患者實現了紅血球輸注獨立，持續八週或更長時間，其中一名患者每天接受 500 毫克，兩名患者每天接受 750 毫克。兩名患者無需輸注紅血球超過六個月，一名患者也獲得了狹窄的完全緩解。輸血獨立性的中位數持續時間為29週。此外，一名輸血負擔較重的患者每天接受 500 毫克治療，獲得了輕微的 HI-E 反應，與基線相比，紅血球輸血減少了 64%。

Looking at PK, we noticed that at R289 doses of 500 mg once daily and higher, R835 plasma concentrations reached or exceeded those correlating with 50% or 90% LPS-induced cytokine inhibition that was previously observed in healthy volunteers. And what's interesting is that at these doses, i.e. 500 margin and 750 mg once daily, 40% or 4 out of 10 of valuable transfusion dependent patients achieve transfusion independence.

透過 PK 研究，我們注意到，當 R289 劑量為每天一次 500 毫克及以上時，R835 血漿濃度達到或超過了先前在健康志願者中觀察到的與 50% 或 90% LPS 誘導的細胞因子抑制相關的濃度。有趣的是，在這些劑量下，即每天一次 500 毫克和 750 毫克，40% 或十分之四的輸血依賴患者實現了輸血獨立。

Moving to slide 19, you see the summary of the responding patients. A few things to highlight here. The majority of responding patients were high transfusion burden at baseline and had received a variety of prior therapies, including luspatercept , hypomethylating agents, and even some experimental therapies. Both patients achieving durable transfusion independence lasting more than 6 months, patients 4 and 10, were high transfusion burden at baseline and had received HMAs.

翻到第 19 張投影片，您會看到有回應的病患的摘要。這裡有幾點要強調。大多數有反應的患者在基線時輸血負擔較高，並且已經接受過多種先前治療，包括luspatercept、低甲基化藥物，甚至一些實驗性療法。兩名患者（患者 4 和患者 10）均實現了超過 6 個月的持久輸血獨立性，他們在基線時的輸血負擔很高，並且接受了 HMA。

Beneath the table, we see the hemoglobin levels over time for the 3 patients that became transfusion-free. Although patient 10 in the middle eventually lost their response following a drug interruption and dose reduction, on the background of transfusion independence, peak hemoglobin increases ranging from 2.3 g to 5.6 g 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，我們可以看到 3 名不再輸血的患者的血紅素水平隨時間的變化。中間的10號病人雖然最終在停藥、減量後失去了治療反應，但在不依賴輸血的背景下，其峰值血紅蛋白較基線增加了2.3~5.6g/分升，提示R289有糾正貧血的潛力，為其在治療早期的評估提供了支持。

In summary, the initial data is encouraging, showing R289 is generally well tolerated with promising signs of preliminary activity and heavily pre-treated transfusion dependent patients. We look forward to sharing additional data from the study in the second half of this year.

綜上所述，初步數據令人鼓舞，顯示 R289 整體耐受性良好，初步活性跡象良好，並且適用於大量預先治療的輸血依賴患者。我們期待在今年下半年分享研究的更多數據。

Now we should focus to olutasidenib, or IDH1 inhibitor. Beginning on slide 21, glioma is an area that is incredibly challenging, where there's not been much advancement in therapeutic options. Diffuse gliomas are the most common primary brain tumor in adults, affecting approximately 20,000 in the US each year. IDH1 mutations occur in about 70% of patients with grade 2 and 3 glioma and are found at up to almost 35% of adolescent and young adult patients. Unfortunately, most of disease recurs, and there is no standard of care therapy for relapsed patients.

現在我們應該關注奧魯他尼，或是IDH1抑制劑。從第 21 張投影片開始，神經膠質瘤是一個極具挑戰性的領域，其治療方案並沒有取得太大的進展。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，而青少年和年輕成年患者則高達近 35% 會出現 IDH1 突變。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法。

The recent approval of vorasidenib, an IDH1 and 2 inhibitor in grade 2 low-grade gliomas, has highlighted the potential for IDH inhibitors in glioma. Olutasidenib was previously evaluated in a Phase 1b/2 study in 26 patients, which was previously published in the journal Neuro Oncology. Two patients with high-grade glioma achieved partial responses, and both with enhancing tumors, and 10 patients achieved stable disease for a disease control rate of 48%. This clinical proof of concept supports further evaluation of olutasidenib glioma.

沃拉西尼（vorasidenib）是一種用於治療 2 級低度膠質瘤的 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。奧魯他地尼先前已在 26 名患者中進行 1b/2 期研究評估，該研究結果已發表在《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，且均伴隨腫瘤增強，10 例患者病情穩定，疾病控制率為 48%。此臨床概念驗證支持對奧魯他尼膠質瘤的進一步評估。

Moving to slide 22, with the outline our development approach in glioma. Last year, we entered a collaboration with the global Neuro-Oncology Consortium Connect. In CONNECT’s target trial, a molecularly guided Phase 2 umbrella clinical trial for high-grade glioma, the Rigel-sponsored arm of the study, TarGeT-D, will evaluate a post-radiotherapy maintenance regimen of olutasidenib in combination with temazolomide, followed by olutasidenib monotherapy. In newly diagnosed patients between 12 and 39 years of age with IDH1 mutation positive high-grade glioma. This study is open for enrollment.

轉到投影片 22，概述了我們在膠質瘤方面的發展方法。去年，我們與全球神經腫瘤學聯盟 Connect 建立了合作關係。在 CONNECT 的目標試驗中，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 將評估奧魯他尼與替馬唑胺聯合治療的放療後維持方案，隨後進行奧魯他尼單藥治療。年齡介於 12 歲至 39 歲之間，新診斷的 IDH1 突變陽性高惡性度膠質瘤患者。此項研究現已開放報名。

In addition, we're on track to initiate a Phase 2 clinical study in recurrent glioma later this year. We think this is an important opportunity as there is a significant unmet need in this patient population. We, along with Connect, are excited about olutasidenib's potential to provide a much-needed new treatment option to this underserved patient population, and we look forward to the data generation from the CONNECT study in addition to our planned study in recurrent glioma.

此外，我們計劃於今年稍後啟動復發性膠質瘤的 2 期臨床研究。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 23, you'll see another important collaboration, our strategic alliance with the MD Anderson Cancer Center, to advance olutasidenib more broadly into AML, MDS, and beyond. All four studies included in this collaboration are open for enrollment, and we look forward to sharing updates from this collaboration in the future.

在第 23 張幻燈片上，您將看到另一項重要合作，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。此次合作涉及的所有四項研究均已開放註冊，我們期待在未來分享此次合作的最新進展。

Turning to our partner program. On slide 25, as Raul mentioned, we're very excited about the Lilly collaboration for ocadusertib and the CNS penetrate program. The RIPK1 Inhibitor Programs are progressing well with our partner Lilly, and we're very pleased with the program's potential. RIPK1 is implicated in a broad range of inflammatory cellular processes and plays a key role in TMF signaling. Ocadusertib, the 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 is advancing well. The pre-clinical CNS penetrant RIPK1 inhibitor program is also progressing for lead candidate nomination.

轉向我們的合作夥伴計劃。在投影片 25 上，正如 Raul 所提到的，我們對禮來公司在 ocadusertib 和 CNS 滲透計畫的合作感到非常興奮。RIPK1 抑制劑專案與我們的合作夥伴禮來公司合作進展順利，我們對該專案的潛力感到非常滿意。RIPK1 與多種發炎細胞過程有關，並在 TMF 訊號傳導中發揮關鍵作用。Ocadusertib 是一種非中樞神經系統滲透性 RIPK1 抑制劑，先前稱為 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。第 2a 階段招生工作進展順利。臨床前中樞神經系統滲透性 RIPK1 抑制劑計畫也正在進行主要候選藥物提名。

Moving to slide 26, we outlined several upcoming milestones for our development programs in 2025. For our ongoing R289 program and lower-risk MDS, we expect to complete the dose escalation part of the Phase 1b study. We then plan to initiate the dose-expansion phase later this year. Also, during the year, we plan to seek health authority input on the registrational path for R289. And we're anticipating presenting updated dose escalation data in the second half of the year.

轉到第 26 張投影片，我們概述了 2025 年發展計畫的幾個即將到來的里程碑。對於我們正在進行的 R289 計劃和低風險 MDS，我們預計將完成 1b 期研究的劑量遞增部分。我們計劃在今年稍後啟動劑量擴展階段。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。我們預計在今年下半年提供更新的劑量遞增數據。

Then for olutasidenib, we plan to initiate a Phase 2 clinical study in recurrent glioma by year end. We'll provide you with more details about that study later this year. In addition, we'll continue to support the four MD Anderson studies and the CONNECT study. We're excited about the potential of our development programs and look forward to providing updates in the future.

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。我們將在今年稍後為您提供有關該研究的更多詳細資訊。此外，我們將繼續支持四項 MD Anderson 研究和 CONNECT 研究。我們對我們的開發計劃的潛力感到興奮，並期待在未來提供更新。

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

現在我們將電話轉給 Dean，討論本季的財務表現。院長。

Thank you, Lisa.

謝謝你，麗莎。

I'm on slide number 28. We reported net product sales of $43.6 million for the first quarter, growth of 68% year over year, including TAVALISSE net product sales of $28.5 million, a growth of 35% year over year, GAVRETO net product sales of $9 million. As a reminder, GAVRETO became available from Rigel in June of 2024. And we reported REZLIDHIA net product sales of $6.1 million, a growth of 25% year over year. Net product sales from TAVALISSE, GAVRETO, and REZLIDHIA were recorded net of estimate discounts, chargebacks, rebates, returns, co-pay assistance, and other allowances of $16.6 million.

我看的是第 28 張投影片。我們報告第一季淨產品銷售額為 4,360 萬美元，年增 68%，其中 TAVALISSE 淨產品銷售額為 2,850 萬美元，年增 35%，GAVRETO 淨產品銷售額為 900 萬美元。提醒一下，GAVRETO 將於 2024 年 6 月由 Rigel 推出。我們報告 REZLIDHIA 淨產品銷售額為 610 萬美元，年增 25%。TAVALISSE、GAVRETO 和 REZLIDHIA 的淨產品銷售額扣除預估折扣、退款、回扣、退貨、共同支付援助和其他津貼後為 1,660 萬美元。

As anticipated, we saw a sequential decrease in net product sales from the fourth quarter of 2024. Consistent with our remarks on our fourth-quarter earnings call and what we've seen in past first quarters, our revenues were impacted by a drawdown in inventory levels across our distribution channels. We also reported $9.8 million in contract revenues from our collaborators for the first quarter. Primarily driven by contributions from Grifols, Kissei, which included the $3 million dollar milestone payment, and Medison, bringing our total revenues for the first quarter to $53.3 million.

正如預期的那樣，我們看到淨產品銷售額從 2024 年第四季開始連續下降。與我們在第四季度收益電話會議上的言論以及過去第一季看到的情況一致，我們的收入受到分銷渠道庫存水準下降的影響。我們還報告了第一季來自合作夥伴的合約收入 980 萬美元。主要得益於 Grifols、Kissei（包括 300 萬美元的里程碑付款）和 Medison 的貢獻，使我們第一季的總收入達到 5330 萬美元。

Finally, I'd like to take a moment to discuss the reporting impact from our notification to Lilly that we will not exercise our opt-in right related to the development and commercialization of ocadusertib for the treatment of non-CNS diseases. As a result of this notification, in the second quarter, we expect to recognize approximately $40 million in collaboration revenue. This is non-cash and related to the release of the remaining cost-share liability currently on our balance sheet. Under the terms of our collaboration agreement, Rigel will continue to be entitled to receive milestone and tiered royalty payments of future net sales.

最後，我想花點時間討論一下我們通知禮來公司將不會行使與用於治療非中樞神經系統疾病的 ocadusertib 的開發和商業化相關的選擇權的報告影響。由於此通知，我們預計第二季將實現約 4,000 萬美元的合作收入。這是非現金，與釋放我們資產負債表上目前剩餘的成本分攤責任有關。根據我們合作協議的條款，Rigel 將繼續有權獲得未來淨銷售額的里程碑和分級特許權使用費。

Moving on to the next slide, and down the income statement and costs and expenses. Our cost of product sales were approximately $4.4 million for the first quarter of 2025. Total cost and expenses were $40.6 million compared to $36.5 million for the same period of 2024. Increasing costs and expenses was mainly due to increased personnel related costs and higher R&D costs driven by the timing of clinical activities related to R289 and olutasidenib. In addition, cost of product sales increased, driven by increased product sales, higher royalties, and amortization of intangible assets. These increases were partially offset by decreased stock-based compensation expense.

進入下一張投影片，查看損益表和成本與費用。2025 年第一季度，我們的產品銷售成本約為 440 萬美元。總成本和費用為 4,060 萬美元，而 2024 年同期為 3,650 萬美元。成本和費用增加主要是由於人員相關成本增加以及與 R289 和 olutasidenib 相關的臨床活動時間導致的研發成本增加。此外，由於產品銷售額增加、特許權使用費增加以及無形資產攤銷，產品銷售成本也有所增加。這些增加部分被股票薪酬費用的減少所抵銷。

We reported net income of $11.4 million for the first quarter compared to a net loss of $8.2 million in the same period in 2024. We ended the quarter with cash, cash equivalents and short-term investments of $77.1 million similar to the $77.3 million as of the end of 2024.

我們報告第一季淨收入為 1,140 萬美元，而 2024 年同期淨虧損為 820 萬美元。本季末，我們的現金、現金等價物和短期投資為 7,710 萬美元，與 2024 年底的 7,730 萬美元相似。

Before I discuss our financial outlook for 2025, I want to spend a moment discussing potential tariffs to Rigel as a result of global trade tensions. Rigel uses a group of typical third-party contract manufacturers for API and finished goods manufacturing, some of which are located outside the US. Given the uncertainty, we're not prepared to provide an expected impact of potential tariffs today. We do expect any impact to be modest and note that our IP is domiciled in the US.

在討論我們 2025 年的財務前景之前，我想花點時間討論一下由於全球貿易緊張局勢而對 Rigel 徵收的潛在關稅。Rigel 使用一組典型的第三方合約製造商進行 API 和成品製造，其中一些位於美國境外。鑑於不確定性，我們今天還沒有準備好提供潛在關稅的預期影響。我們確實預計任何影響都是適度的，並注意到我們的知識產權位於美國。

Turning to our financial outlook for 2025, we continue to anticipate total revenue in the range of approximately $200 million to $210 million. This includes our unchanged expectation of approximately $185 million to $192 million in net product sales and $15 million to $18 million of contract revenues from collaborations. In addition, we continue to anticipate reporting positive net income for the full year of 2025, while funding existing and new clinical development programs. Please note that our 2025 revenue guidance excludes the approximately $40 million in non-cash collaboration revenue that's expected to be recognized in the second quarter related to our agreement.

展望 2025 年的財務展望，我們繼續預期總收入將在約 2 億美元至 2.1 億美元之間。這包括我們對淨產品銷售額約 1.85 億美元至 1.92 億美元的不變預期以及合作合約收入 1500 萬美元至 1800 萬美元的不變預期。此外，我們繼續預計 2025 年將全年實現正淨收入，同時為現有和新的臨床開發項目提供資金。請注意，我們的 2025 年收入指引不包括預計在第二季確認的與我們的協議相關的約 4,000 萬美元的非現金合作收入。

To wrap up my section, we look forward to continuing financial discipline for the remainder of 2025 and beyond. With I'd like to turn the call back over to Raul. Raul.

總結我的部分，我們期待在 2025 年剩餘時間及以後繼續保持財務紀律。我想把電話轉回勞爾。勞爾。

Thank you, Dean. Moving on to slide 30, we made significant strides over the past three years to expand our commercial portfolio via unlicensing or acquiring assets that fit our commercial capabilities and portfolio focus.

謝謝你，迪恩。翻到第 30 張投影片，過去三年來，我們透過取消授權或收購符合我們商業能力和投資組合重點的資產，在擴大我們的商業投資組合方面取得了重大進展。

We have a proven track record of delivering top-line growth, as evidenced by the 32% compound annual growth rate, or CAGR in revenue growth from 2021 to 2024. This revenue growth enables us to fund our business and our strategic priorities, including to continue expanding our hematology and oncology business. And we're confident in our expectation of approximately $185 million to $192 million in net product sales this year.

我們在實現營收成長方面有著良好的記錄，2021 年至 2024 年 32% 的複合年增長率（CAGR）就是明證。收入成長使我們能夠為我們的業務和策略重點提供資金，包括繼續擴大我們的血液學和腫瘤學業務。我們對今年淨產品銷售額約 1.85 億美元至 1.92 億美元的預期充滿信心。

Turning to slide 31. For the remainder of 2025, our priorities are clear. Grow our commercial business, advance our development pipeline, identify new pipeline opportunities, and continue to maintain financial discipline. We anticipate growing our net product sales in 2025 by approximately 30% year over year.

翻到第 31 張投影片。對於 2025 年剩餘時間，我們的優先事項很明確。發展我們的商業業務，推動我們的開發管道，發現新的通路機會，並繼續保持財務紀律。我們預計 2025 年我們的淨產品銷售額將年增約 30%。

We remain focused on advancing our Phase 1b clinical study, evaluating R289 for the treatment of patients with lower-risk MDS. And we are on track to publish updated data at a medical meeting late this year and initiate the dose-expansion phase of this study by year end. For olutasidenib, we plan to initiate a new Rigel-sponsored Phase 2 study in recurring glioma while continuing to support our strategic collaborations with both MD Anderson and the Connect organization.

我們將繼續專注於推進我們的 1b 期臨床研究，評估 R289 對低風險 MDS 患者的治療效果。我們計劃在今年稍後的醫學會議上發布最新數據，並在年底前啟動研究的劑量擴展階段。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，同時繼續支持我們與 MD Anderson 和 Connect 組織的策略合作。

With our anticipated strong revenue growth, financial discipline in 2025, we will continue to invest in our development programs but also expect to report positive net income for the full year. Finally, on slide 32, our successful execution of our corporate strategy has resulted in Rigel being uniquely positioned in building a leading hematology and oncology business in a profitable and sustainable manner.

由於我們預計 2025 年收入將強勁增長，財務紀律嚴明，我們將繼續投資於我們的開發計劃，同時也預計全年淨收入將為正。最後，在第 32 張投影片上，我們成功執行了公司策略，這使得 Rigel 在以盈利和可持續的方式建立領先的血液學和腫瘤學業務方面佔據了獨特的地位。

And with that, I'd like to thank you for your interest, and we will now open the call to your questions. Operator.

最後，我要感謝您的關注，我們現在開始回答您的問題。操作員。

(Operator Instructions)

（操作員指示）

Kalpit Patel, B. Riley Securities.

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

Yeah, hey, good afternoon and thanks for taking the question. I had one on the TarGet-D the program that you have ongoing in high-grade glioma. I guess you have two different plans here for glioma. You have that study running and then you also have the planned company-sponsored Phase 2 trial and recurrent glioma. Can you help us clarify the objectives and perhaps the design differences between the two and longer term, what signal do you want to see in the TarGeT-D program to justify moving forward in one program or the other.

是的，嘿，下午好，感謝您回答這個問題。我參加了 TarGet-D 項目，該項目正在針對高級別膠質瘤進行研究。我猜你們針對神經膠質瘤有兩種不同的計畫。您正在進行這項研究，然後還計劃進行公司贊助的第二階段試驗和復發性膠質瘤試驗。您能否幫助我們澄清目標以及兩者之間的設計差異？從長遠來看，您希望在 TarGeT-D 計劃中看到什麼訊號來證明推進一個計劃或另一個計劃是合理的。

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

我會讓麗莎嘗試一下，而且，我認為，這兩個——這是開始，這裡有兩項不同的研究，兩個不同的患者群體。我們很高興看到 TarGeT-D 計劃，這是一項已經在進行的整體研究，這使我們能夠將我們的產品添加到其中。因此從邏輯上來說，這有助於啟動這項研究。與我們在自己的臨床研究中考慮的人群略有不同。

Maybe, Lisa, you can add more color on this.

也許，麗莎，你可以為此添加更多色彩。

Yeah, sure. Thanks for the question.

是的，當然。謝謝你的提問。

So, yes, Raul mentioned, we're supporting the CONNECT umbrella study. Our arm is looking at the combination of, as I mentioned, olutasidenib with temozolomide as maintenance. So in the maintenance settings, so these will be targeting patients that are post-surgery and radiotherapy. So it's temozolomide, olutasidenib for one year, followed by one more year of olutasidenib monotherapy maintenance. And this is going to be focused on patients with grade 3 astrocytoma. So looking for an impact on progression-free survival.

是的，正如 Raul 所提到的，我們支持 CONNECT 總體研究。正如我所提到的，我們正在研究奧魯他尼與替莫唑胺的組合作為維持治療。因此在維護設置中，這些將針對手術和放射治療後的患者。因此，使用替莫唑胺和奧魯他尼治療一年，然後再進行一年的奧魯他尼單藥治療維持。這將重點關注 3 級星狀細胞瘤患者。因此尋找對無惡化存活期的影響。

We're happy to be, working with Connect on this one. It's a unique population. These are adolescents and young adults. We're looking to kind of help expand that site at the sites also because they're a pediatric organization potentially into more adult sites, and we think it complements our strategy nicely with our plans to go into recurrent glioma. Now we're not, discussing any of the details about our plans yet, but we will be sharing more about that, later on in the year.

我們很高興能與 Connect 合作。這是一個獨特的族群。這些人是青少年和年輕人。我們希望幫助擴大該站點，因為它們是一個兒科組織，有可能擴展到更多的成人站點，我們認為它與我們進入復發性膠質瘤的計劃很好地補充了我們的策略。現在我們還沒有討論有關我們計劃的任何細節，但我們將在今年稍後分享更多相關資訊。

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

好的，太棒了。然後，關於您與 Annora 就 TAVALISSE 解決的專利訴訟，我想問一個簡單的問題。我想問一下，還有其他 ANDA 申請人需要投資者註意嗎？

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

不。據我們所知，沒有 ANDA 申請人。

Okay, perfect. Thank you very much for taking the question.

好的，完美。非常感謝您回答這個問題。

Thank you, Kalpit.

謝謝你，卡爾皮特。

Joe Pantginis, H.C. Wainwright.

喬潘特吉尼斯、H.C. 溫賴特。

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

大家好，下午好。感謝您回答這個問題。首先，當您查看產品銷售情況時，很高興看到 TAVALISSE 的核心收入持續擴大，GAVRETO 有所增加，您會看到 - REZLIDHIA 略有增加，TAVALISSE 略有下降。

So I guess any commentary with regard to typical first-quarter resets. Are you seeing what you expected and what I'm getting at here is, the turbulence in the environment right now and yeah, I'll put in quotes drama around people trying to understand what might be happening with regard to Medicare changes as well.

所以我猜想任何有關典型的第一季重置的評論。您是否看到了您所期望的情況？我在這裡要說的是，目前環境動盪不安，是的，我會加上引號，人們試圖了解醫療保險改革方面可能發生的事情。

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

是的，為什麼不呢，戴夫，也許你可以發表評論，我知道迪恩對此也有評論。

Sure, thanks for the question, Joe. Actually, for Q1, we're quite pleased with our progress on all three brands. We grew demand for all three brands. And so I think we're right where we want to be, which is why we're sticking with our guidance, and, I think, our signs for Q1, obviously, we did go into it kind of prepared for the changes, particularly with respect, to the Inflation Reduction Act.

當然，謝謝你的提問，喬。實際上，就第一季而言，我們對三個品牌的進展都非常滿意。我們對這三個品牌的需求都有成長。所以我認為我們正處於我們想要的狀態，這就是我們堅持指導的原因，而且我認為，我們第一季的跡象表明，顯然我們確實為變化做好了準備，特別是關於《通貨膨脹削減法案》的變化。

And I think we did a really, the team did a terrific job making sure that patients understood the changes and all of the factors that would enable them to have medications at the beginning of the year. And I think we pulled that through quite successfully and our demand continued to grow.

我認為我們確實做得非常好，團隊做了出色的工作，確保患者了解這些變化以及使他們能夠在年初獲得藥物的所有因素。我認為我們非常成功地實現了這一目標，並且我們的需求持續成長。

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

是的，我認為戴夫說得對，所以我們對需求方面感到滿意，而且我們確實看到庫存預期下降，但仍然實現了 68% 的同比增長，所以這對我們來說是一個強勁的季度。

Right, thanks for the info.

好的，謝謝你的資訊。

Thank you, Joe.

謝謝你，喬。

(Operator Instructions)

（操作員指示）

Farzin Haque, Jefferies.

傑富瑞的 Farzin Haque。

Hi, thank you for taking my question. I had a couple, I guess I'll start with the R289. Are you saying more on how you're setting expectations for the split doses that you're exploring post ash like with the dose level 5 and 6? And then just to clarify for advancing to the recommended Phase 2 dose, would you need regulatory feedback on those escalation data sets?

你好，謝謝你回答我的問題。我有幾個，我想我會從 R289 開始。您是否更多地談論瞭如何設定您正在探索的灰燼後分割劑量的預期，例如劑量等級 5 和 6？然後，為了澄清推進到建議的第 2 階段劑量，您是否需要有關這些升級資料集的監管回饋？

Yeah, I'll let Lisa to comment.

是的，我會讓麗莎發表評論。

On that. Yeah, thank you for the question.

就此而言。是的，謝謝你的提問。

So in terms of -- we don't really have any expectations, but I'm not sure I understand the question. We have switched -- I'll provide an answer and you can tell me if I've answered it satisfactorily. We switched some time ago from once daily to twice daily dosing because we thought that, biologically, it makes more sense to maintain a tonic suppression of inflammation as opposed to having this once daily like peak and trough and peak and trough in terms of from that aspect. And that's why we switched to explore the BID dosing.

因此就——我們實際上沒有任何期望，但我不確定我是否理解了這個問題。我們已經轉換了——我會提供答案，你可以告訴我我是否回答得令人滿意。我們前段時間將劑量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，維持對發炎的強直抑制比每天一次的峰值和低谷更有意義。這就是我們轉而探索 BID 劑量的原因。

We're progressing up. We had some preliminary data on the 250 BID, we, we've now completed enrollment of the 500, 250 and now, into the 500 BID. So as I mentioned, we're going to be, updating data at ASH share that with you later on this year. I think, we'll share some PK data as well that I think will contribute to what I mentioned in terms of it may be better to kind of have that more prolonged exposure as opposed to the up and down.

我們正在進步。我們掌握了 250 BID 的一些初步數據，現在我們已經完成了 500、250 以及 500 BID 的招生工作。正如我所提到的，我們將在今年稍後更新 ASH 的數據並與您分享。我認為，我們也會分享一些 PK 數據，我認為這將有助於我所提到的，即與上下波動相比，進行更長的曝光可能會更好。

With respect to the, you mentioned the alignment or how to select the doses. So as you're aware, the FDA has encouraged companies now to align with Project Optimus to ensure more robust dose selection early before advancing into Phase 2. So consistent with that, we will be seeking input from the FDA aligning with them on the two doses for comparison in the dose escalation part of the study, and we'll be doing that mid-year.

關於這一點，您提到了對齊或如何選擇劑量。因此，如您所知，FDA 現在鼓勵公司與 Optimus 專案保持一致，以確保在進入第 2 階段之前儘早進行更穩健的劑量選擇。因此，與此一致，我們將尋求 FDA 的意見，與他們就兩種劑量進行協調，以便在研究的劑量遞增部分進行比較，我們將在年中完成這項工作。

Got it. That makes sense. And then for follow up on the earlier question on the ANDA filing, so [EOA] is one example, and they cannot enter the market. I think it mentioned prior to 2Q '32. But if there are additional ANDA filers in the future, could they have an earlier market entry or is that 2Q32 pretty much when you should begin new entry?

知道了。這很有道理。然後跟進先前關於 ANDA 申請的問題，[EOA] 就是一個例子，他們不能進入市場。我認為它提到了 1932 年第二季之前的情況。但是，如果未來有更多的 ANDA 申請人，他們是否可以更早進入市場，或者 2032 年第二季是否應該是開始新進入的時間？

Yeah, you can get second ANDA filers and they would need to defeat the patents which in order to enter the market earlier than the current last list of patents, which would be July of 27, 2032. But there's a possibility of an ANDA filer, but once there's one entrant already which is a settlement, it's a disincentive to second filers and tertiary filers, but it is technically possible that there could be a second filer.

是的，您可以獲得第二個 ANDA 申請人，他們需要擊敗專利，以便比目前最新的專利清單更早進入市場，即 2032 年 7 月 27 日。但有可能出現 ANDA 申請人，但一旦已經有一個申請人達成和解，就會對第二個申請人和第三個申請人產生不利影響，但從技術上講，可能會有第二個申請人。

No, we have not, there's no, we have no, notice of a second filer.

不，我們沒有，沒有，我們沒有第二個申報人的通知。

Got it. Thank you.

知道了。謝謝。

Sure.

當然。

Thank you, Farzin.

謝謝你，法爾津。

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

謝謝，現在沒有其他問題了。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。謝謝。

Thank you. I'd like to thank everyone for joining us on the call today.

謝謝。我要感謝大家今天參加我們的電話會議。

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

這是非常強勁的一年的開始。第一季對我們來說是一個出色的季度。我們對本季所取得的成績感到非常滿意。這為我們實現強勁的一年奠定了良好的基礎。因此，我要感謝您對 Rigel 的持續關注。我還要感謝我們的員工對 Rigel 和我們的價值觀的承諾，特別是我們對改善病患生活的承諾。隨著時間的推移，我們將及時向您通報未來的通話情況。祝您有美好的一天。

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

謝謝。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。