Rigel Pharmaceuticals Inc (RIGL) 2025 Q2 法說會逐字稿

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

問候並歡迎參加 Rigel Pharmaceuticals 2025 年第二季財務電話會議。（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。弗瑞先生，您可以開始了。

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

歡迎參加我們 2025 年第二季財務業績和業務更新電話會議。2025 年第二季的財務新聞稿剛剛發布，您可以在 rigel.com 上的投資者關係網站的「新聞與活動」部分中與本次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. 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 Q2 quarterly report on Form 10-Q on file with the SEC.

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的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最新的截至 2024 年 12 月 31 日的 10-K 表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 表第二季度季度報告。

Any forward-looking statements are made only as of today's date, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I'd like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez. Raul?

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。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 us 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，也謝謝大家今天加入我們。今天與我一起出席的還有我們的首席商務官戴夫·桑托斯 (Dave Santos)、我們的首席醫療官麗莎·羅伊克賈爾 (Lisa Rojkjaer) 和我們的首席財務官迪恩·肖爾諾 (Dean Schorno)。

Beginning on slide 4, I will provide an overview of Rigel's accomplishments across the business and our financial results for the second quarter of 2025. Let me start by saying that this was a really great quarter for Rigel. We continue to make significant progress on the execution of our corporate strategy. For those not familiar with Rigel, our focus is on growing our hematology and oncology business through commercial execution, advancing our pipeline, product in-licensing and acquisition, and financial discipline.

從第 4 張投影片開始，我將概述 Rigel 在整個業務中取得的成就以及我們 2025 年第二季的財務表現。首先我要說的是，對於 Rigel 來說，這是一個非常棒的季度。我們在執行公司策略方面持續取得重大進展。對於那些不熟悉 Rigel 的人來說，我們的重點是透過商業執行、推進我們的產品線、產品許可和收購以及財務紀律來發展我們的血液學和腫瘤學業務。

With this in mind, in the second quarter, we achieved net product sales of more than $58 million, an increase of 76% year over year and our best quarter ever. This all-time high was driven by our growing commercial portfolio and increased sales across all our commercial products. Dave will provide a more detailed update on our three products and their second-quarter contributions later on in the call.

考慮到這一點，第二季度，我們實現了超過 5,800 萬美元的淨產品銷售額，年增 76%，是我們有史以來最好的季度。這段歷史最高紀錄得益於我們不斷成長的商業產品組合以及所有商業產品銷售額的成長。戴夫將在稍後的電話會議中提供有關我們的三款產品及其第二季度貢獻的更詳細的更新。

Total revenue for the second quarter was $101.7 million, including $42.7 million in contract revenues from collaborations. As I discussed during our May call, we notified Lilly that we would not exercise our right to share in future development expenses for ocadusertib, Rigel's RIPK1 inhibitor, previously known as R552. As a result, we recognized $40 million in non-cash revenue in the second quarter. Dean will discuss the accounting of this in his remarks.

第二季總營收為 1.017 億美元，其中包括 4,270 萬美元的合作合約收入。正如我在 5 月電話會議上所討論的那樣，我們通知禮來公司，我們不會行使分享 ocadusertib（Rigel 的 RIPK1 抑制劑，以前稱為 R552）未來開發費用的權利。因此，我們在第二季實現了 4,000 萬美元的非現金收入。迪恩將在他的演講中討論這個問題。

Now, let's talk about our development opportunities. We're excited about the potential of our development pipeline and our ability to fund the clinical development of R289 and olutasidenib. R289, our novel and selective dual IRAK1/4 inhibitor is currently being evaluated in a Phase 1b clinical study in patients with relapsed or refractory lower-risk MDS. We completed enrollment in the dose escalation part of the study in July and expect to share updated data from the study later on this year. Lisa will walk us through the latest updates on our development pipeline.

現在我們來談談我們的發展機會。我們對我們的開發管道的潛力以及我們資助 R289 和 olutasidenib 臨床開發的能力感到非常興奮。R289 是我們新型選擇性雙重 IRAK1/4 抑制劑，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。我們於 7 月完成了該研究劑量遞增部分的招募，並預計將於今年稍後分享該研究的最新數據。Lisa 將向我們介紹我們開發流程的最新進展。

While we focus on our internal development, we're also excited about the potential of ocadusertib a potent oral and selective inhibitor of RIPK1 and Lilly's efforts to advance this molecule. In parallel with growing our commercial business and expanding our development pipeline, we remain committed to pursuing additional in-licensing deals or acquisitions of assets that fit our capabilities commercially and our product focus, such as we've already done successfully with both REZLIDHIA and GAVRETO. Underscoring these efforts is an emphasis on maintaining financial discipline or making the clinical development investments.

在我們專注於內部開發的同時，我們也對 ocadusertib（一種強效口服和選擇性 RIPK1 抑制劑）的潛力以及禮來公司推進這種分子的努力感到興奮。在發展我們的商業業務和擴大我們的開發管道的同時，我們仍然致力於尋求更多的授權交易或收購符合我們商業能力和產品重點的資產，例如我們已經在 REZLIDHIA 和 GAVRETO 上成功做到了這一點。強調這些努力的是強調保持財務紀律或進行臨床開發投資。

This has resulted in both top line and bottom line growth and allowed us to generate $59.6 million in net income and to increase our cash balance to more than $108 million in the second quarter.

這導致了營業收入和利潤的雙雙增長，並使我們在第二季度創造了 5,960 萬美元的淨收入，並將現金餘額增加到 1.08 億美元以上。

Moving on to slide 5. You'll see the growth of our net product sales year over year. We have consistently delivered top line growth, as evidenced by the 32% compound annual growth rate or CAGR from 2021 to 2024. Year to date, in 2025, we have generated $102.5 million in net product sales. This is nearly the same net sales that we generated for the full year of 2023, and so a tremendous start to this year.

轉到投影片 5。您會看到我們的淨產品銷售額逐年成長。我們持續實現營收成長，2021 年至 2024 年 32% 的複合年增長率 (CAGR) 就是明證。截至目前，也就是 2025 年，我們的淨產品銷售額已達 1.025 億美元。這幾乎與我們 2023 年全年的淨銷售額相同，因此今年的開局非常好。

We are now raising our total revenue guidance in 2025 to between $270 million and $280 million from the previous range of $200 million and $210 million, which includes net product sales of $210 million to $220 million, an increase from the prior range of $185 million to $192 million. This new outlook reflects anticipated growth of 45% to 52% compared to 2024, exceeding the roughly 30% growth rate that we delivered over the last few years.

我們現在將 2025 年的總收入預期從先前的 2 億至 2.1 億美元上調至 2.7 億至 2.8 億美元之間，其中包括 2.1 億至 2.2 億美元的淨產品銷售額，高於先前的 1.85 億至 1.92 億美元。這項新展望反映出與 2024 年相比預計將成長 45% 至 52%，超過了過去幾年我們實現的約 30% 的成長率。

Rigel is in a unique position as a self-sustaining company with the added benefit of a promising pipeline of assets. We remain focused on the execution of our corporate strategy in continuing our progress throughout 2025 and beyond.

Rigel 作為一家能夠自給自足的公司，擁有獨特的優勢，並且擁有前景廣闊的資產管道。我們將繼續專注於執行我們的企業策略，在 2025 年及以後繼續取得進步。

Now with that, I will turn the call over to Dave to provide more information on our commercial business for you. Dave?

現在，我將把電話轉給戴夫，以便為您提供有關我們商業業務的更多資訊。戴夫？

Thank you, Raul. On slide 7, you'll see our three commercial products: TAVALISSE, GAVRETO, and REZLIDHIA. Moving the slide 8, we are thrilled to report another excellent quarter from our commercial portfolio, marked by strong year-over-year growth and an all-time high in revenues in the second quarter of 2025. You can see on the slide how our quarterly and annual net product sales have increased since 2021.

謝謝你，勞爾。在第 7 張投影片上，您將看到我們的三種商業產品：TAVALISSE、GAVRETO 和 REZLIDHIA。翻到第 8 張投影片，我們很高興地報告，我們的商業投資組合又迎來了一個出色的季度，其特點是強勁的同比增長和 2025 年第二季度收入創歷史新高。您可以在投影片上看到自 2021 年以來我們的季度和年度淨產品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 second quarter of 2024, we reported $33.5 million and now for the second quarter of 2025, we generated $58.9 million. Our second-quarter results reflect accelerated demand through improved patient affordability in 2025, augmented by favorable growth-to-net dynamics, which drove a 76% increase year over year.

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 年第二季度，我們的營收為 3,350 萬美元，而 2025 年第二季度，我們的營收為 5,890 萬美元。我們第二季的業績反映出，2025 年患者負擔能力的提高將加速需求成長，加上有利的淨成長動態，推動需求年增 76%。

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 demand for REZLIDHIA.

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產品組合後提高 GAVRETO 的知名度，並提高對 REZLIDHIA 的需求。

Slide 9 shows a summary of our commercial performance by product. First on TAVALISSE. I'm pleased to report another record quarter in which we generated $40.1 million in net product sales, an increase of 52% compared to the second quarter of 2024. This growth was driven by continued strong new patient demand with another consecutive quarterly record high, and increased carryover demand from new patients that started therapy in prior quarters.

投影片 9 顯示了我們按產品劃分的商業表現摘要。首先是 TAVALISSE。我很高興地報告本季又創下新高，我們的淨產品銷售額為 4,010 萬美元，與 2024 年第二季相比成長了 52%。這一增長得益於持續強勁的新患者需求（連續一個季度創下歷史新高）以及前幾季度開始治療的新患者的結轉需求增加。

For GAVRETO, we delivered $11.8 million in net product sales in Q2. As a reminder, in the second quarter of 2024, we recorded $1.9 million of revenue as GAVRETO just became commercially available from Rigel in late June of 2024. On a sequential basis, we saw 32% revenue growth versus the first quarter of 2025. As we continue to see an increase in new patients and carryover demand. We are focused on driving awareness of GAVRETO and ensuring patients are educated on the latest treatment guidelines that recommend the use of a RET inhibitor in the front-line setting.

對於 GAVRETO，我們在第二季實現了 1,180 萬美元的淨產品銷售額。提醒一下，2024 年第二季度，我們錄得 190 萬美元的收入，因為 GAVRETO 剛在 2024 年 6 月下旬由 Rigel 上市。與 2025 年第一季相比，我們的營收季增了 32%。隨著我們不斷看到新患者和結轉需求的增加。我們致力於提高人們對 GAVRETO 的認識，並確保患者了解建議在前線環境中使用 RET 抑制劑的最新治療指南。

And lastly for REZLIDHIA, we reported $7 million in net product sales, an increase of 36% compared to the prior year period, reflecting demand growth. We continue to focus on educating healthcare providers about the potential benefits of REZLIDHIA for patients with relapsed or refractory IDH1 mutant AML.

最後，對於 REZLIDHIA，我們報告的淨產品銷售額為 700 萬美元，與去年同期相比成長了 36%，反映了需求的成長。我們將繼續致力於教育醫療保健提供者了解 REZLIDHIA 對復發或難治性 IDH1 突變型 AML 患者的潛在益處。

Driving awareness of the efficacy data for REZLIDHIA in the post-venetoclax setting, which we believe is important to physicians, continues to be a key priority for us. We also believe we have compelling data for the earlier use of REZLIDHIA in mIDH1 patients who relapse or are refractory to front line therapy. To that end, at ASCO in June, we presented data for patients who received REZLIDHIA after either one to two lines of therapy, or three or more lines of prior therapy.

我們認為，提高人們對 REZLIDHIA 在維奈克拉治療後療效數據的認識對醫生來說非常重要，這仍然是我們的首要任務。我們也相信，我們擁有令人信服的數據，證明 REZLIDHIA 可早期用於復發或對第一線治療有抵抗力的 mIDH1 患者。為此，我們在 6 月的 ASCO 上展示了接受過一至兩種療法或三種或更多種療法治療後接受 REZLIDHIA 治療的患者的數據。

Patients in the one to two prior regimens group showed a higher overall response rate, and longer median overall survival than those who had three or more prior lines of therapy, providing a rationale for initiating treatment with REZLIDHIA earlier in the relapsed or refractory treatment paradigm. This supporting data shows why we believe we have significant opportunity to grow REZLIDHIA in relapsed or refractory IDH1 mutant AML.

與接受過三種或三種以上先前療法的患者相比，接受過一至兩種先前療法的患者總體反應率更高，中位總體生存期更長，這為在復發或難治性治療模式中更早開始使用 REZLIDHIA 治療提供了理論依據。這些支持數據顯示了為什麼我們相信我們在復發或難治性 IDH1 突變型 AML 中擁有發展 REZLIDHIA 的巨大機會。

Overall, we're very pleased by our commercial performance in the second quarter, and I would like to express our sincere thanks to the entire team for their outstanding performance in Q2.

總體而言，我們對第二季的商業表現感到非常滿意，並向整個團隊在第二季的出色表現表示誠摯的感謝。

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 TAVLESSE, and in Canada and Israel via partners, Kissei, Grifols and Medison. In addition, our partners continue to pursue regulatory approvals for TAVALISSE and new markets. Most recently, in early July, Kissei's licensing partner, JW Pharmaceutical Corporation, launched TAVALISSE in South Korea.

轉到第 10 張投影片，我們繼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 和新市場的監管批准。最近，7 月初，Kissei 的授權合作夥伴 JW Pharmaceutical Corporation 在韓國推出了 TAVALISSE。

For REZLIDHIA in 2024, we expanded our relationship with Kissei to include several countries in Asia for all potential indications, and we entered into an exclusive license agreement with Dr. Reddy's for all potential indications throughout Dr. Reddy's territory. We are pleased that access to our products is expanding outside the US, and we continue to explore other opportunities for partnerships to bring our products to other markets around the globe.

對於 2024 年的 REZLIDHIA，我們擴大了與 Kissei 的關係，將所有潛在適應症涵蓋到亞洲的幾個國家，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，我們也將繼續探索其他合作機會，將我們的產品推向全球其他市場。

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. I'm on slide 12. Our hematology and oncology pipeline strategy is focused on the clinical development of R289, our novel duo IRAK1/4 inhibitor in lower-risk myelodysplastic syndrome, or MDS, and the expansion of olutasidenib beyond relapsed or refractory IDH1 mutated AML and into other cancers with IDH1 mutations such as recurrent glioma.

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。我在第 12 張投影片。我們的血液學和腫瘤學管道策略專注於 R289 的臨床開發，這是我們針對低風險骨髓增生異常綜合徵 (MDS) 的新型雙 IRAK1/4 抑製劑，以及將奧魯他尼擴展到復發或難治性 IDH1 突變 AML 之外以及其他具有 IDH1 突變的癌症，例如復發性膠質瘤。

Beginning with R289, our Phase 1b study in patients with relapsed or refractory lower-risk MDS is progressing well, and enrollment in the dose escalation part of the study was completed in July. We plan to share updated dose escalation data later this year. We remain on track to initiate the dose expansion part of the study in the second half of the year, which will be a randomized comparison of two doses of R289 in order to select the recommended Phase 2 dose for future studies.

從 R289 開始，我們針對復發或難治性低風險 MDS 患者進行的 1b 期研究進展順利，該研究的劑量遞增部分的招募已於 7 月完成。我們計劃在今年稍後分享更新的劑量遞增數據。我們仍計劃在今年下半年啟動研究的劑量擴展部分，該部分將對兩種劑量的 R289 進行隨機比較，以便為未來的研究選擇建議的 2 期劑量。

For olutasidenib, we believe it has potential in several cancers where mutated IDH1 plays a role. Regarding our partners, olutasidenib is being evaluated as maintenance therapy in IDH1 mutation positive glioma by the CONNECT Cancer Consortium, and in IDH1 mutation positive AML and low and high-risk MDS by MD Anderson. We remain open to additional opportunities or collaborations to evaluate olutasidenib and IDH1 mutated cancers.

對於奧魯他尼，我們相信它在幾種突變 IDH1 中發揮作用的癌症中具有潛力。關於我們的合作夥伴，CONNECT 癌症聯盟正在將奧魯他尼評估為 IDH1 突變陽性膠質瘤的維持療法，MD Anderson 正在將奧魯他尼評估為 IDH1 突變陽性 AML 和低風險和高風險 MDS 的維持療法。我們仍然對評估奧魯他尼和 IDH1 突變癌症的更多機會或合作持開放態度。

Rigel also remains focused on evaluating potential acquisition and in-licensing opportunities that strategically fit our hematology and oncology portfolio and infrastructure. We're focused on evaluating differentiated assets in hematology, oncology, or related areas that are late-stage programs.

Rigel 也將繼續專注於評估策略上適合我們的血液學和腫瘤學產品組合和基礎設施的潛在收購和許可機會。我們專注於評估血液學、腫瘤學或相關領域的後期項目的差異化資產。

Now we'll spend a few moments on R289, our dual IRAK1/4 inhibitor. On slide 14, I'd like to spend a few minutes reviewing the value proposition of R289 and lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the US. There's a high unmet need for therapies in this disease area, particularly for transfusion-dependent patients.

現在我們將花一些時間研究我們的雙重 IRAK1/4 抑制劑 R289。在第 14 張投影片上，我想花幾分鐘回顧 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。此疾病領域的治療需求很高，特別是對於依賴輸血的患者。

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 normal hematopoiesis. R835, the active moiety of R289, blocks toll-like receptor and IL-1 receptor signaling in vitro and was active in various pre-clinical 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正常造血。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表現出活性。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 fast track and orphan drug designation from the FDA, 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, the unmet need of the patient population, and the FDA's willingness to collaborate with Rigel in the development of R289.

提醒一下，目前正在臨床評估的 R289 是一種口服前藥，可在腸道中快速轉化為 R835。R289 擁有 FDA 的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、患者群體的未滿足需求以及 FDA 願意與 Rigel 合作開發 R289。

In addition, R289 has thus far demonstrated a promising clinical profile in a Phase 1b study. The initial dose escalation data that were presented at last year's ASH annual meeting, demonstrated promising preliminary safety and clinical activity in elderly heavily pretreated patients with relapsed or refractory lower-risk MDS. While I'm here, I wanted to mention that we noted that with the recent data cut, there was a change in status for one patient previously reported with a minor response. That is a reduction in the number of red cell transfusions by more than 50% compared to the baseline.

此外，R289 迄今為止在 1b 期研究中表現出良好的臨床表現。去年 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 的老年大量接受過治療的患者，該藥物具有良好的初步安全性和臨床活性。在這裡，我想提一下，我們注意到，隨著最近的數據削減，先前報告的一名輕微反應的患者的狀態發生了變化。與基線相比，紅血球輸注次數減少了 50% 以上。

We discovered that this patient had received additional red cell transfusions that were not entered into the database at the time of the initial analysis. Thus, this patient is no longer considered a responder. I'll discuss the study design in a moment.

我們發現該患者接受了額外的紅血球輸注，但在初步分析時並未輸入資料庫。因此，該患者不再被視為有反應者。我稍後會討論研究設計。

On slide 15, I'd like to update you on several key milestones for the program that we're focused on this year. First, as mentioned, we completed enrollment in the dose escalation part of our ongoing Phase 1b study in July. We remain on track to initiate the dose expansion phase in the second half of this year, potentially within the third quarter.

在第 15 張投影片上，我想向您介紹我們今年重點關注的計畫的幾個關鍵里程碑。首先，如上所述，我們在 7 月完成了正在進行的 1b 期研究的劑量遞增部分的招募。我們仍有望在今年下半年啟動劑量擴展階段，可能在第三季內。

We recently engaged with the FDA to discuss the dose expansion phase and to seek preliminary input on a potential path to registration. We're aligned with the FDA on the dose expansion part of the study, and will provide more details on the registrational path following completion of the Phase 1b study, and once we've aligned with the agency on the design of our pivotal study. And lastly, we look forward to sharing updated data from the study later in the year.

我們最近與 FDA 接洽，討論劑量擴展階段並尋求有關潛在註冊途徑的初步意見。我們在研究的劑量擴展部分與 FDA 保持一致，並將在完成 1b 期研究後以及在關鍵研究的設計上與該機構保持一致後提供有關註冊路徑的更多詳細資訊。最後，我們期待在今年稍後分享該研究的最新數據。

On the next slide, I'll review the study design. This is our multi-center open label Phase 1b study in patients with relapsed refractory lower-risk MDS that are either transfusion dependent or have symptomatic anemia. Initial data from the study was presented at ASH in late 2024. The study aims to evaluate the safety, PK, and preliminary efficacy of R289 in this patient population, as well as select a dose for future studies. It includes a dose escalation part utilizing a modified 3 plus 3 design evaluating 6 dose regimens of R289, and the dose expansion phase, which will compare two doses of R289 head to head in order to select the recommended Phase 2 dose.

在下一張投影片中，我將回顧研究設計。這是我們針對依賴輸血或有症狀性貧血的複發難治性低風險 MDS 患者進行的多中心開放標籤 1b 期研究。該研究的初步數據於 2024 年底在 ASH 上公佈。該研究旨在評估 R289 在該患者群體中的安全性、PK 和初步療效，以及選擇未來研究的劑量。它包括一個劑量遞增部分，利用改進的 3 + 3 設計來評估 R289 的 6 種劑量方案，以及劑量擴展階段，該階段將比較兩種劑量的 R289，以選擇建議的第 2 階段劑量。

Once this occurs, we'll open up a cohort of patients to explore upfront dosing of R289, patients that are relapsed, refractory to, or ineligible for ESAs.

一旦發生這種情況，我們將開放一批患者，探索 R289 的前期劑量，這些患者是復發的、對 ESA 有抵抗力的或不適合使用 ESA 的患者。

Slide 17, I'd like to talk about 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 quality of life.

投影片 17，我想談談低風險 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。對患者的主要後果是貧血和輸血依賴，這會對生活品質產生不利影響。

In addition, infections, iron overload from transfusions, and subsequent organ dysfunction, all negatively impact the patient. Therapies used in the upfront setting include erythropoiesis stimulating agents, or ESAs, if patients are eligible, or luspatercept. Luspatercept and more recently, imetelstat, are also approved for ESA failure transfusion dependent, lower-risk MDS patients.

此外，感染、輸血引起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。如果患者符合條件，前期使用的療法包括紅血球生成刺激劑（ESA）或luspatercept。Luspatercept 和最近的 imetelstat 也被批准用於治療 ESA 失敗輸血依賴性、低風險 MDS 患者。

Finally, hypomethylating agents or HMAs are also approved. However, the percentage of patients achieving transfusion independence is low. With eight-week transfusion independence rates approaching 40% with luspatercept and imetelstat, there's still a need for safe, effective therapies for transfusion dependent lower-risk MDS patients that are relapsed refractory to or ineligible for ESAs.

最後，低甲基化劑或HMA也獲得批准。然而，實現輸血獨立的患者比例很低。使用 luspatercept 和 imetelstat 治療後，八週的輸血獨立率已接近 40%，但對於復發性、對 ESA 有抵抗力或不適合使用 ESA 的輸血依賴性低風險 MDS 患者，仍需要安全有效的治療方法。

Now I should focus to our strategic collaborations. As I've mentioned, we have collaborations in place with CONNECT and MD Anderson to evaluate olutasidenib and other cancers harboring IDH1 mutations. I'm now on slide 19.

現在我應該集中討論我們的策略合作。正如我所提到的，我們已經與 CONNECT 和 MD Anderson 合作，評估 olutasidenib 和其他攜帶 IDH1 突變的癌症。我現在在第 19 張投影片。

CONNECT is a global pediatric neuro-oncology consortium that we entered into a collaboration with last year. And CONNECT's target trial, a molecularly guided Phase 2 umbrella clinical trial for high grade glioma, the Rigel-sponsored arm of the study called TarGeT-D, will evaluate a post radiotherapy maintenance regimen of olutasidenib in combination with temozolomide, followed by the olutasidenib monotherapy in newly diagnosed patients between 12 and 39 years of age with IDH1 mutation positive high-grade glioma.

CONNECT 是一個全球兒科神經腫瘤學聯盟，我們去年與其建立了合作關係。CONNECT 的目標試驗是針對高級別膠質瘤的分子引導 2 期傘狀臨床試驗，也是該研究由 Rigel 贊助的分支，名為 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 歲之間新診斷的 IDH1 突變陽性高級別膠質瘤患者進行奧魯他尼單藥治療。

This study is open for enrollment. In addition to this collaboration with CONNECT, we continue to look at other opportunities to expand our studies of IDH1 mutated cancers through our own studies or collaborative partners, including a potential Rigel-led Phase 2 glioma study. We, along with CONNECT, are excited about olutasidenib's potential to provide a much-needed new treatment option to this underserved patient population with significant unmet need.

此項研究現已開放報名。除了與 CONNECT 的合作之外，我們還將繼續尋找其他機會，透過我們自己的研究或合作夥伴來擴大我們對 IDH1 突變癌症的研究，包括潛在的由 Rigel 領導的 2 期神經膠質瘤研究。我們和 CONNECT 一樣，對奧魯他尼為這一醫療資源匱乏、需求嚴重未得到滿足的患者群體提供急需的新治療選擇的潛力感到興奮。

On slide 20, we summarize our strategic alliance with the MD Anderson Cancer Center to advance olutasidenib more broadly into AML, MDS, and beyond. All four studies in this collaboration are open for enrollment, and we look forward to sharing updates in the future.

在第 20 張投影片上，我們總結了與 MD 安德森癌症中心的策略聯盟，以將奧魯他尼更廣泛地應用於 AML、MDS 及其他領域。此次合作的所有四項研究均已開放註冊，我們期待未來分享最新進展。

Now, I'll pass the call to Dean to discuss our partnered program with Eli Lilly and our financial results for the quarter. Dean?

現在，我將把電話轉給 Dean，討論我們與禮來公司的合作計劃以及本季的財務表現。院長？

Thank you, Lisa. I'm on slide 22. Before I review our financial results for the quarter, I want to provide a brief update on our collaboration with Lilly and the related impact of our financial statements during the quarter. The RIPK1 inhibitor programs are progressing well, and we're excited about the program's potential.

謝謝你，麗莎。我在第 22 張投影片。在回顧本季的財務表現之前，我想先簡單介紹一下我們與禮來公司的合作以及本季財務報表的相關影響。RIPK1 抑制劑專案進展順利，我們對該專案的潛力感到興奮。

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. Enrollment in a Phase 2a study is ongoing. The preclinical CNS penetrant RIPK1 inhibitor program is also progressing toward lead candidate nomination. As Raul mentioned, we notified Lilly that we will not exercise our opt-in right related to the development and commercialization of ocadusertib.

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 名患有活動性中度至重度類風濕性關節炎的患者進行適應性 2a、2b 期臨床試驗。階段 2a 研究的招募正在進行中。臨床前中樞神經系統滲透性 RIPK1 抑制劑計畫也正在朝著主要候選藥物提名的方向發展。正如 Raul 所提到的，我們通知禮來公司，我們不會行使與 ocadusertib 的開發和商業化相關的選擇加入權。

As a result, we recognize $40 million in collaboration revenue in the second quarter. This is non-cash and related to the release of the remaining cost share liability that was on our balance sheet. Note that under the terms of our collaboration agreement, Rigel will continue to be entitled to receive milestones and tiered royalty payments of future net sales.

因此，我們在第二季實現了 4000 萬美元的合作收入。這是非現金，與釋放我們資產負債表上的剩餘成本分攤責任有關。請注意，根據我們的合作協議條款，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 our financials. I'm on slide number 24. We reported net product sales of $58.9 million for the second quarter, a growth of 76% year over year, including TAVALISSE net product sales of $40.1 million, a growth of 52% year over year. GAVRETO net product sales of $11.8 million. As a reminder, GAVRETO became commercially available from Rigel in late June of 2024 and we reported $1.9 million of revenue for the second quarter of 2024. Lastly, we reported REZLIDHIA net product sales of $7 million, a growth of 36% year over year.

繼續討論我們的財務狀況。我在第 24 號投影片。我們報告第二季淨產品銷售額為 5,890 萬美元，年成長 76%，其中 TAVALISSE 淨產品銷售額為 4,010 萬美元，較去年同期成長 52%。GAVRETO 淨產品銷售額為 1,180 萬美元。提醒一下，GAVRETO 於 2024 年 6 月下旬由 Rigel 上市，我們報告 2024 年第二季的營收為 190 萬美元。最後，我們報告 REZLIDHIA 淨產品銷售額為 700 萬美元，年增 36%。

Our net product sales were recorded net estimate discounts, chargebacks, rebates, returns, copay assistance, and other allowances of $20.7 million. We also reported $42.7 million in contract revenues from our collaborations for the second quarter, primarily consisting of the $40 million of non-cash revenue from Lilly, as well as contributions from Grifols, Kissei, and Medison related to delivery of drugs supply and earned royalties, bringing our total revenues for the second quarter to $101.7 million.

我們的淨產品銷售額記錄了淨估計折扣、退款、回扣、退貨、共同支付援助和其他津貼，金額為 2,070 萬美元。我們還報告了第二季度來自合作的合約收入 4,270 萬美元，主要包括來自禮來的 4,000 萬美元非現金收入，以及 Grifols、Kissei 和 Medison 在藥品供應和所得特許權使用費方面的貢獻，使我們第二季的總收入達到 1.017 億美元。

Moving to slide 25 and down the income statement to costs and expenses. Our cost of product sales were approximately $4.5 million for the second quarter of 2025. Total cost and expenses were $40.6 million compared to $36.4 million for the same period of 2024. The increase in cost and expenses are mainly due to higher cost of product sales, increased research and development costs driven by the timing of clinical activities related to olutasidenib and R289, and higher personnel related costs, and stock-based compensation expense.

移至第 25 張投影片，並將損益表向下移動到成本和費用。2025 年第二季度，我們的產品銷售成本約為 450 萬美元。總成本和費用為 4,060 萬美元，而 2024 年同期為 3,640 萬美元。成本及費用的增加主要由於產品銷售成本增加、奧魯替尼和R289相關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股票薪酬費用增加。

We reported net income of $59.6 million for the second quarter compared to a net loss of $1 million in the same period in 2024. We ended the quarter with cash, cash equivalent, and short-term investments of $108.4 million compared to $77.3 million as of the end of 2024.

我們報告第二季淨收入為 5,960 萬美元，而 2024 年同期淨虧損為 100 萬美元。本季末，我們的現金、現金等價物和短期投資為 1.084 億美元，而 2024 年底為 7,730 萬美元。

Turning into our financial outlook for 2025. We're raising our total revenue guidance to approximately $270 million to $280 million, an increase from our prior range of $200 million to $210 million. This includes updated net product sales expectations are approximately $210 million to $220 million, an increase from the prior range of $185 million to $192 million and contract revenues from collaborations of approximately $60 million, an increase from the prior range of $15 million to $18 million.

轉向我們對 2025 年的財務展望。我們將總收入預期從先前的 2 億至 2.1 億美元上調至約 2.7 億至 2.8 億美元。其中包括更新後的淨產品銷售額預期約為 2.1 億美元至 2.2 億美元，高於先前的 1.85 億美元至 1.92 億美元，以及合作合約收入約為 6,000 萬美元，高於先前的 1,500 萬美元至 1,800 萬美元。

The updated total revenues and contract revenues from collaborations, expectations are inclusive of the $40 million in non-cash contract revenue related to Rigel's agreement with Lilly. In addition, we continue to anticipate that we will report positive net income for the full year 2025, while funding existing and new clinical development programs.

更新後的總收入和合作合約收入預期包括與 Rigel 與禮來公司協議相關的 4000 萬美元非現金合約收入。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。

To wrap up my section, we look forward to continued financial discipline for the remainder of 2025 and beyond.

最後，我們期待在 2025 年剩餘時間及以後繼續保持財務紀律。

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. And moving on to slide 26. To reiterate, we have made significant advancements over the last several years in expanding our hematology and oncology business. We have consistently delivered meaningful top line growth, enabling us to fund our business and strategic priorities. We have now raised our net product sales expectations for 2025 and now expect to generate 45% to 52% year-over-year growth, an increase from the roughly 30% growth that we delivered in the prior four years.

謝謝你，迪恩。繼續看第 26 張投影片。重申一下，過去幾年我們在擴大血液學和腫瘤學業務方面取得了重大進展。我們始終如一地實現有意義的營收成長，這使我們能夠為我們的業務和策略重點提供資金。我們現在已經提高了 2025 年的淨產品銷售額預期，預計將年增 45% 至 52%，高於前四年約 30% 的成長率。

Moving on to slide 27. For the remainder of the year, we continue to focus on increasing sales of our three commercial products and delivering on our revenue guidance. We are committed to advancing our Phase 1b clinical study evaluating R289 for the treatment of patients with lower-risk MDS. We plan to share updated data by your end, and potentially initiate the dose expansion phase of the study in the third quarter.

轉到第 27 張投影片。在今年剩餘的時間裡，我們將繼續專注於增加三種商業產品的銷售並實現我們的收入預期。我們致力於推進評估 R289 治療低風險 MDS 患者的 1b 期臨床研究。我們計劃與您分享更新的數據，並可能在第三季啟動研究的劑量擴展階段。

For olutasidenib, we plan to continue progress to initiate a Rigel-sponsored Phase 2 study in recurring glioma, while supporting our strategic collaborations with the CONNECT organization, as well as MD Anderson. We will also continue to look for opportunities to expand our product portfolio through in-license and/or acquisition of synergistic late-stage assets.

對於 olutasidenib，我們計劃繼續推進，啟動由 Rigel 贊助的複發性膠質瘤 2 期研究，同時支持我們與 CONNECT 組織以及 MD Anderson 的策略合作。我們也將繼續尋找機會透過授權和/或收購協同後期資產來擴大我們的產品組合。

With our anticipated strong revenue growth and continued financial discipline, Rigel is well positioned for the near term and for the long term. In closing on slide 28, Rigel has delivered a strong first half of 2025, and we are focused on continuing that momentum throughout the remainder of the year. Our proven strategy has built Rigel into a profitable, growing, and sustainable business.

憑藉我們預期的強勁收入成長和持續的財務紀律，Rigel 在短期和長期內都處於有利地位。在第 28 張幻燈片結束時，Rigel 在 2025 年上半年表現強勁，我們致力於在今年剩餘時間內繼續保持這一勢頭。我們行之有效的策略已將 Rigel 打造為一家獲利、成長且永續發展的企業。

With that, I'd like to thank you for your interest, and we will now open the call to your questions. Back to you, operator.

非常感謝您的關注，現在我們將開始回答您的問題。回到你這裡，接線生。

(Operator Instructions) Joe Pantginis, H.C. Wainwright.

（操作員指示）Joe Pantginis、H.C. Wainwright。

Hi, everybody, thanks for taking the questions. So great growth here, nice blocking and tackling on GAVRETO and REZLIDHIA. Excuse me for the pronunciation, I just -- with regard to TAVALISSE, it looks like it saw a very nice inflection, obviously, with regard to the 52% growth. You mentioned obviously it's due to new patient demand and increase of carryover. Just curious, can you split up the percentages contribution to this growth here?

大家好，感謝你們回答問題。這裡進步很大，GAVRETO 和 REZLIDHIA 的阻擋和鏟球都很好。請原諒我的發音，我只是 - 關於 TAVALISSE，它看起來似乎出現了非常好的變化，顯然，就 52％ 的增長而言。您提到這顯然是由於新患者的需求和結轉的增加。只是好奇，您能分一下對這一增長的貢獻百分比嗎？

Dave, can you comment on that? Thank you, Joe, thank you for the question.

戴夫，你能對此發表評論嗎？謝謝你，喬，謝謝你的提問。

Yeah, great question, and I will say that particularly in the first half of the year, we did have more new patient starts than ever before, so our percentage of our growth due to new patients starts was higher. And I think you heard me say in my prepared remarks that that was accelerated by improved patient affordability in 2025.

是的，這個問題問得很好，我想說的是，特別是在今年上半年，我們確實接待了比以往更多的新患者，因此，由於新患者而帶來的增長百分比更高。我想你們已經聽到我在準備好的發言中說過，2025 年病患負擔能力的提升將加速這一進程。

No, that's great. And just curious like what level of surprise is that? And I'm sort of playing devil's advocate, surprised that you have about that growth and the affordability versus a potential bear case out there that TAVALISSE has reached a level of steady state.

不，那太好了。我只是好奇那是什麼程度的驚喜？我有點像是扮演魔鬼代言人，很驚訝你對這種成長和可負擔性的看法與潛在的熊市情況相反，TAVALISSE 已經達到了穩定狀態。

Well, listen, we have been planning to continue to grow TAVALISSE. So we remain focused on new patient growth. And what did happen this year as you know, it's the coverage gap, was eliminated in 2025 due to the Inflation Reduction Act, and we knew that this could potentially help us this year because, as you know, Part D drugs or oral drugs, what happened in the past is patients would enter into that coverage gap, particularly at the beginning of the year, and it would be difficult for them to access product.

好吧，聽著，我們一直在計劃繼續發展 TAVALISSE。因此，我們仍然關注新患者的成長。如您所知，今年發生的情況是，由於《通貨膨脹削減法案》，覆蓋範圍的缺口在 2025 年被消除，我們知道這可能會對我們今年有所幫助，因為如您所知，對於 D 部分藥物或口服藥物，過去發生的情況是患者會進入覆蓋範圍的缺口，特別是在年初，他們很難獲得產品。

And this year, with a $2,000 annual out-of-pocket cap for patients and their ability to potentially evenly smooth those payments out through the year, they have much easier ability to access a drug like TAVALISSE, an oral agent, and I think we were prepared to ensure that patients -- that we were ready to address this change at the beginning of the year.

今年，患者每年的自付費用上限為 2,000 美元，而且他們可以在全年平均分攤這些費用，因此他們可以更輕鬆地獲得像 TAVALISSE 這樣的口服藥物，我認為我們已經準備好確保患者——我們在年初就準備好應對這一變化。

And so, I will say that we've always been focused on new patient starts. Is it potentially a little more benefit from improved affordability than we had anticipated? I'm not sure I would say that, but I think the team executed extremely well, and because we have a portfolio of oral therapies, I think the entire portfolio benefited from improved affordability in 2025. And that also helped us improve our gross to net dynamics.

所以，我想說，我們一直專注於新患者的開始。負擔能力的提高是否可能為我們帶來比我們預期更多的利益？我不確定我是否會這麼說，但我認為團隊表現得非常好，而且由於我們擁有一系列口服療法，我認為整個產品組合將受益於 2025 年可負擔性的提高。這也幫助我們改善了總收入與淨收入的動態。

So really, it's a confluence of those things. So it's a confluence of those things, Joe, and I think we were well aware of this coming in and well prepared to it. So it required both of those things to know it's coming, to know what you're going to do about it, and we executed, I'd say, very well in the first half of the year. Many of those patients carry over into subsequent quarters and what used to be difficult Q1s in the past, this IRA has helped that and needless to say, more patients are getting drugs that perhaps in the past couldn't have gotten them because of the change. So that's a good thing overall.

所以實際上，這是這些事物的融合。所以這是這些事情的匯合，喬，我認為我們很清楚這一點，並且做好了充分的準備。所以，我們需要這兩件事來了解它的到來，知道你要做什麼，我想說，我們在今年上半年執行得非常好。許多患者會進入隨後的季度，而過去第一季往往比較困難，而 IRA 對此有所幫助，不用說，由於這一變化，更多的患者可以獲得過去可能無法得到的藥物。總的來說這是一件好事。

No, fantastic. Appreciate all the added color and very nice to see.

不，太棒了。欣賞所有添加的顏色，看起來非常漂亮。

Yigal Nochomovitz, Citigroup.

花旗集團的 Yigal Nochomovitz。

Hey, guys, congrats on a nice progress commercially and on the pipeline. I'm curious about the comment regarding the 32% CAGR which you noted from '21 to '24 and then the apparent inflection higher, potentially higher, 45% to 52%. Is the statement that this is the expectation sort of for the business on a go-forward basis not only this year but into '26 and beyond? Is it, are we on a new sort of trajectory here or how would you frame that inflection point in terms of thinking about the longer-term performance of the business?

嘿，夥計們，祝賀你們在商業和管道方面取得了良好的進展。我對您提到的從 21 年到 24 年的 32% 複合年增長率以及隨後的明顯拐點（可能更高，為 45% 到 52%）的評論感到好奇。這是否意味著這是對未來業務的期望，不僅是今年，而且是 26 年及以後？我們是否正處於一種新的軌跡上，或者從業務的長期表現來看，您如何定義這個轉折點？

Yeah, I could take that, but I'll also ask Dave to comment on that. This has been a fantastic start to the year, and I think things have happened. Dynamics, David just explained a few of them that occurred earlier in this year that I think gave us a boost, but the underlying business had been growing quite nicely, 32% year on year on TAVALISSE specifically a strong performer throughout those years, even though it's been on the market already. So really, a confluence of various things drove this increase in sales this year.

是的，我可以接受，但我也會請戴夫對此發表評論。這是今年的一個美好的開始，我認為事情已經發生了。動態，大衛剛剛解釋了今年早些時候發生的一些事情，我認為這給了我們推動力，但基礎業務一直在增長相當不錯，特別是 TAVALISSE 同比增長 32%，這些年來表現強勁，儘管它已經上市了。所以實際上，多種因素共同推動了今年銷售額的成長。

We haven't given guidance beyond this year, other than to say we continue to expect growth in the business, and we continue to have confidence that the product provides meaningful value to these patients. And now we can get -- make sure that more of them benefit from these products, being that they're oral, in particular, and so we're very enthusiastic about what's to come.

我們沒有給出今年以後的指導，只是說我們繼續預期業務會成長，我們仍然相信該產品能為這些患者提供有意義的價值。現在我們可以確保更多的人從這些產品中受益，特別是口服產品，因此我們對未來的發展充滿熱情。

And I think a good, great first half of the year, the best ever, and we expect the dynamics to not change dramatically going forward.

我認為今年上半年表現非常好，是有史以來最好的，我們預計未來情況不會有巨大變化。

Yeah, Raul, I would just add that we've got a growing business, obviously. We have been laser focused on ensuring patients have the opportunity to try TAVALISSE, REZLIDHIA, or GAVRETO depending on what the clinician -- which type of patient the clinician has, and we do everything possible to make sure we're efficient in that targeting and I think what you're seeing is our ability to grow revenues with very little incremental cost on a three-product portfolio, and that's exactly what we're executing on.

是的，勞爾，我只想補充一點，我們的業務顯然正在成長。我們一直專注於確保患者有機會根據臨床醫生的情況（臨床醫生的患者類型）嘗試 TAVALISSE、REZLIDHIA 或 GAVRETO，並且我們盡一切可能確保我們能夠有效地實現這一目標，我想您所看到的是我們能夠通過三種產品組合以很少的增量成本來增加收入，而這正是我們正在執行的。

Looking at our impactable opportunities, targeting those and with laser-like focus and going out and getting it, so yes, we definitely plan to continue to grow new patients starts and demand as we move forward.

看看我們可產生影響的機會，瞄準這些機會，像雷射一樣集中註意力，然後出去爭取，所以是的，我們絕對計劃在前進的過程中繼續增加新患者的開始和需求。

You also note the leverage in the business. We have a stable, good quality commercial organization that really has delivered in the past, and now you add additional products to it, and you see the economic benefit of that.

您也注意到業務中的槓桿作用。我們擁有一個穩定、優質的商業組織，它在過去確實發揮了重要作用，現在您可以為其添加更多產品，並且您可以看到其帶來的經濟效益。

Okay, thanks. And then I had a few more specific questions on glioma and the oluta development. What more can you say with respect to the Phase 2 design, how would you do that study? What would be the right comparator arm?

好的，謝謝。然後我又問了幾個關於神經膠質瘤和膠質瘤發展的具體問題。關於第二階段的設計您還能說些什麼？您將如何進行這項研究？正確的比較臂是什麼？

And then regarding the work you're doing with this CONNECT and the TarGeT-D trial, if that looks good, what would you do with the data? Is that something you could then use to for submission in pediatrics? Or would you need to then pursue another company-sponsored study to take that pediatric segment to the market?

然後關於您在 CONNECT 和 TarGeT-D 試驗中所做的工作，如果看起來不錯，您會如何處理數據？您是否可以將其用於兒科提交？或者您需要進行另一項由公司贊助的研究，以將兒科領域推向市場？

That's Lisa to comment on on those two.

這是麗莎對這兩個人的評論。

Yeah. Thanks, Raul, and thanks for the question, Yigal. So regarding our plans for glioma, we will be disclosing more about the design of the study in recurrent glioma probably later this year once we're -- we're not yet in the position to do that, but stay tuned.

是的。謝謝，勞爾，也謝謝伊加爾提出的問題。因此，關於我們針對神經膠質瘤的計劃，我們可能會在今年稍後披露更多有關復發性神經膠質瘤研究的設計 - 我們尚未準備好這樣做，但請繼續關注。

And for the CONNECT study, that's a very good question as well. There, we still have to discuss a little bit more with CONNECT and potentially with the agency on a potential for looking at that to support a filing. We haven't done any of that yet. I don't anticipate that we would be doing an additional study in that same space.

對於 CONNECT 研究來說，這也是一個非常好的問題。在那裡，我們仍然需要與 CONNECT 進行更多討論，並可能與該機構討論是否有可能支持提交申請。我們還沒有做任何這些事情。我並不認為我們會在同一領域進行額外的研究。

Okay, got you. Thank you very much.

好的，明白了。非常感謝。

Farzin Haque, Jefferies.

法爾津·哈克（Farzin Haque），傑富瑞集團。

Hi, this is Amin on for Farzin. Congrats on the quarter and thank you for taking our questions. A couple of questions from us well. Based on what you're seeing so far in 3Q in numbers of bottles shipped and the IRA impact, how does that shape your thinking around the guidance going forward? And are there any anticipated headwinds or tailwinds specifically around TAVALISSE sales and GAVRETO at this point? And I have a follow-on.

大家好，我是 Farzin 的 Amin。恭喜本季取得的成績，並感謝您回答我們的問題。我們有幾個問題。根據您目前看到的第三季出貨瓶數和 IRA 的影響，這對您對未來指引的思考有何影響？目前，TAVALISSE 和 GAVRETO 的銷售方面是否有預期的阻力或順風？我還有一個後續問題。

That's Dave to comment on that.

戴夫對此發表了評論。

So we just grew, if you take the six months that we just completed, and you look at the six months prior to that or the back half of 2024. We just grew 20% revenues -- in revenues. And in our guidance at the midpoint of our guidance, we're still projecting double-digit growth in our revenues, and at the top end, about 15%. So we are expecting growth to continue. And when I said that about improved affordability dynamics in the first half of the year, as I said, in my earlier remarks, the coverage gap was really an issue at the beginning of the year when patients hadn't been on medications and they were restarting the clock, and that was the time the donut hole experience was more.

所以，如果你看一下我們剛剛過去的六個月，再看看之前的六個月或 2024 年下半年，我們就實現了成長。我們的收入剛剛增長了 20%。在我們的預測中點，我們仍然預計收入將實現兩位數成長，最高成長約為 15%。因此我們預計成長將會持續。當我談到上半年可負擔能力動態的改善時，正如我在之前的評論中所說的那樣，覆蓋範圍的差距確實是年初的一個問題，當時患者還沒有服藥，他們正在重新開始服藥，而那時甜甜圈洞的體驗更為嚴重。

So we do expect that as we move into the second half of the year, there are fewer patients that kind of fall into that. So we're -- I don't think the impact of that will be as strong in the second half of the year. I hope that helps.

因此，我們確實預計，隨著進入下半年，出現這種情況的患者會減少。所以，我認為下半年的影響不會那麼大。我希望這能有所幫助。

It's very helpful. How much impact are you seeing on the gross net for the three drugs with the Part D?

這非常有幫助。您認為 D 部分對這三種藥物的總淨值有多大影響？

So we haven't been specific on the gross to net. I will say that from a gross to net consideration, there's a variety of factors. There's the -- we made some distribution channel changes we talked about in the back half of last year, so that's had an effect and a favorable effect of the mix. Mix also impacts gross to net, and there's some favorability, as Dave said, with respect to the IRA adjustments.

因此，我們還沒有具體說明總額與淨額的比例。我想說的是，從整體考慮到淨考慮，有各種各樣的因素。我們對去年下半年討論過的分銷管道進行了一些改變，這對組合產生了積極的影響。混合也會影響總額與淨額，正如戴夫所說，對於 IRA 調整而言，存在一些有利因素。

And then on a go-forward basis, the mix and some of the programs we do will have an impact on gross to net, so we haven't been specific on the individual products, but we expect to see some favorable growth in that as we've seen in the last couple of quarters persist.

然後，從未來來看，我們的產品組合和一些項目將對毛利與淨利產生影響，因此我們還沒有具體說明個別產品的情況，但我們預計會看到一些有利的成長，正如我們在過去幾個季度所看到的那樣。

Thank you very much.

非常感謝。

(Operator Instructions) Kristen Kluska, Cantor Fitzgerald.

（操作員說明）Kristen Kluska、Cantor Fitzgerald。

Hi, this is Ayan on Kristen's line. Thank you for taking our questions. I understand that the primary goal in treating low risk MDS is to reduce or eliminate transfusion dependence. What have you heard from physicians on the degree of transfusion reduction or in dependence that is actually considered clinically meaningful in this setting?

大家好，我是 Kristen 的 Ayan。感謝您回答我們的問題。我了解治療低風險 MDS 的主要目標是減少或消除輸血依賴。您從醫生那裡聽說了哪些關於輸血減少程度或依賴程度的說法，這些說法在這種情況下實際上被認為具有臨床意義？

Yeah, I could take that. I mean, as I mentioned in my prepared remarks, the approvals of luspatercept and imetelstat were based on a transfusion in the eight-week transfusion independence rate of around 38% to 40% for both agents. So there's -- around 60% of the patients are still not benefiting. So I think that there's still room for improvements in this area and with hypomethylating agents that were approved around 25 years ago, it's really not much better.

是的，我可以接受。我的意思是，正如我在準備好的演講中提到的那樣，luspatercept 和 imetelstat 的批准是基於兩種藥物八週輸血獨立率約為 38% 至 40%。因此，大約 60% 的患者仍然沒有受益。因此，我認為該領域仍有改進的空間，而對於大約 25 年前批准的低甲基化藥物來說，情況確實沒有好多少。

So lots of room to improve. So I don't know that the physicians are -- I think anything above this is people would be looking forward to, and also, considering those agents, there are also associated toxicities and a bit of an inconvenience with the root of administration. So I think aside from the activity there, there's also room for improvement and administration.

因此還有很大的進步空間。所以我不知道醫生們——我認為任何高於這個水平的藥物都是人們所期望的，而且，考慮到這些藥物，它們也存在相關的毒性，並且在給藥方面也有一些不便。所以我認為除了那裡的活動之外，還有改進和管理的空間。

Thank you, understood.

謝謝，明白了。

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.

謝謝。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，請他發表最後評論。

Well, thank you. I'd like to be grateful for your attendance to this call and you're interest in Rigel. I think this first half of the year, we've really have delivered well and are extremely proud on what we've been able to accomplish both in the commercial business. The financial position of the company is much stronger today and stronger than, I believe, it's ever been and really good advancements also in terms of our product portfolio.

好的，謝謝你。非常感謝您參加本次電話會議以及您對 Rigel 的興趣。我認為今年上半年我們確實表現良好，並且對我們在商業業務中所取得的成就感到非常自豪。我相信，公司目前的財務狀況比以往任何時候都要強勁，而且我們的產品組合也取得了良好的進步。

So for that, I'd like to thank the employees of Rigel and their dedication to what we're trying to accomplish here. This was a substantial step forward this first half of the year and we look forward to continuing that. Take care.

因此，我要感謝 Rigel 的員工以及他們為我們在這裡所要實現的目標所做的奉獻。這是今年上半年向前邁出的實質一步，我們期待繼續這樣做。小心。

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。