Geron Corp (GERN) 2025 Q1 法說會逐字稿

Hello and welcome to the Geron's first-quarter 2025 early learning conference. (Operator Instructions)

您好，歡迎參加 Geron 2025 年第一季早期學習會議。（操作員指示）

I would now like to turn the conference over to Ron Moldaver, Investor Relations. You may begin.

現在我想將會議交給投資者關係部門的 Ron Moldaver。你可以開始了。

Good morning, everyone. Welcome to the Geron Corporation's first-quarter 2025 earnings conference call. Before we begin, please note that during the course of this presentation and question-and-answer session, we will be making forward-looking statements regarding future events, performance, plans, expectations, and other projections, including those related to the launch, commercial opportunity, and therapeutic potential of RYTELO, anticipated clinical and commercial events and related timelines, the sufficiency of Geron's financial resources, and other statements that are not historical facts.

大家早安。歡迎參加 Geron Corporation 2025 年第一季財報電話會議。在我們開始之前，請注意，在本次演示和問答環節中，我們將對未來事件、業績、計劃、期望和其他預測做出前瞻性陳述，包括與 RYTELO 的發布、商業機會和治療潛力、預期的臨床和商業事件及相關時間表、Geron 財務資源的充足性以及其他非歷史事實的陳述。

Actual events or results could differ materially. Therefore, I refer you to the discussion under the heading risk factors in Geron's most recent periodic report with the SEC, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statement and our future updates to those risk factors. Geron undertakes no duty or obligation to update our forward-looking statements.

實際事件或結果可能有重大差異。因此，我請您參閱 Geron 向美國證券交易委員會提交的最新定期報告中關於風險因素的討論，其中指出了可能導致實際結果與前瞻性聲明中的結果存在重大差異的重要因素以及我們對這些風險因素的未來更新。Geron 不承擔更新我們的前瞻性聲明的義務或責任。

With that, I'll turn the call over to Dawn Bir, Interim President and Chief Executive Officer.

說完這些，我將把電話轉給臨時總裁兼執行長 Dawn Bir。

Good morning. Thank you, Ron, and thank you all for joining us. I'll begin on slide 4. I'm joined today by several members of Geron's management team: Michelle Robertson, our Chief Financial Officer; Jim Ziegler, our Chief Commercial Officer; and Dr. Joseph Eid, our Executive Vice President of Research and Development.

早安.謝謝你，羅恩，也謝謝大家加入我們。我將從第 4 張投影片開始。今天與我一起出席的還有 Geron 管理團隊的幾位成員：我們的財務長 Michelle Robertson；我們的商務長 Jim Ziegler；以及我們的研發執行副總裁 Joseph Eid 博士。

Let's continue on the next slide. I'll begin by stating that RYTELO US commercial launch success is our number one corporate priority. RYTELO is a first-in-class novel telomerase inhibitor recently approved for the treatment of certain patients with lower-risk MDS, a disease with significant unmet need. We believe that there is a large US market opportunity for RYTELO, and Q1 sales were not where we expect them to be.

我們繼續下一張投影片。首先我要說的是，RYTELO 美國商業發布成功是我們公司的首要任務。RYTELO 是一種一流的新型端粒酶抑制劑，最近獲準用於治療某些低風險 MDS 患者，這種疾病存在嚴重未滿足的醫療需求。我們相信 RYTELO 在美國市場擁有龐大的發展機會，但第一季的銷售額並未達到我們的預期。

Q1 RYTELO net revenues were $39.4 million, down $8 million from Q4, while demand in the 13-week period through the week ending March 28 was relatively flat at plus 1% versus the prior 13 weeks. The lower quarter-over-quarter net revenue is due to the inventory drawdown among our distributors from Q4 into Q1. Michelle will address this in greater detail in our financial update.

RYTELO 第一季淨收入為 3,940 萬美元，比第四季下降 800 萬美元，而截至 3 月 28 日當週的 13 週內需求與前 13 週相比基本持平，增長 1%。季度淨收入較上一季下降的原因是我們的經銷商從第四季到第一季的庫存減少。米歇爾將在我們的財務更新中更詳細地討論這個問題。

Personally, I stepped into this role because I'm excited by the opportunity to bring this important medicine to eligible patients and the healthcare community and, together with this leadership team, execute on this commercial opportunity and drive value for all involved.

就我個人而言，我擔任這個職務是因為我很高興有機會將這種重要的藥物帶給符合條件的患者和醫療保健界，並與這個領導團隊一起抓住這個商業機會，為所有參與者創造價值。

Today, we'll share key factors that we believe have influenced the recent SOP performance, as well as specific enhancements we've made and continue to make to support US commercial success. We expect our increased commercial investments to bolster uptake across a broader group of prescribers and drive long-term demand.

今天，我們將分享我們認為影響近期 SOP 表現的關鍵因素，以及我們為支持美國商業成功而做出並將繼續做出的具體改進。我們預計，我們增加的商業投資將促進更廣泛的處方群體的接受度並推動長期需求。

Since our last earnings call, we've performed an in-depth analysis of our commercial efforts with the current market, and we're focused on three key strategies to invigorate sales growth. First, we are investing additional resources to increase brand awareness among the highest-decile US hematologists, treating the greatest number of lower-risk MDS patients today.

自上次財報電話會議以來，我們對當前市場的商業努力進行了深入分析，並專注於三大關鍵策略來促進銷售成長。首先，我們正在投入額外的資源來提高美國最高等級血液學家的品牌知名度，目前他們治療最多的低風險 MDS 患者。

Second, we're refining our marketing and medical efforts to enhance prescribing clarity and competence with the use of RYTELO, articulating how and where to use it successfully, as indicated in our approved label, with the goal of supporting positive HCP and patient experiences and continued use. And third, we're implementing programs to expand US KOL support and advocacy through aligned messaging, education, and through both commercial and medical affairs engagement efforts.

其次，我們正在改進我們的行銷和醫療工作，以提高使用 RYTELO 的處方清晰度和能力，闡明如何以及在何處成功使用它，正如我們批准的標籤中所示，目的是支持積極的 HCP 和患者體驗和持續使用。第三，我們正在實施計劃，透過一致的訊息傳遞、教育以及商業和醫療事務參與努力來擴大美國 KOL 的支持和宣傳。

Today, Jim and Joe will share further details of specific commercial and medical affairs actions to implement these three key strategies. This includes refined HCP target identification, expanded sales and medical field headcount, and the addition of newly created goals to highlight only a few.

今天，Jim 和 Joe 將分享更多實施這三大關鍵策略的具體商業和醫療事務行動的細節。其中包括完善的 HCP 目標識別、擴大銷售和醫療領域員工人數，以及增加新創建的目標（僅突出其中幾個）。

We're confident that by intensifying our focus on the strong execution of launch fundamentals, that we'll see performance trends moving in the right direction and are encouraged by a few recent early performance indicators that we will share with you today.

我們相信，透過加強對發布基礎的強力執行，我們將看到性能趨勢朝著正確的方向發展，我們今天將與您分享的一些近期早期性能指標也讓我們感到鼓舞。

Success takes an organized team effort, and we've invested with deliberate attention and urgency to reinvigorate this launch. With our recent EU approval in March, we are pursuing what we believe is a targeted, disciplined path to make RYTELO available to patients beyond the United States while being fiscally responsible.

成功需要有組織的團隊努力，我們投入了深思熟慮的注意力並迫切希望重振這次發布。隨著我們在 3 月獲得歐盟批准，我們正在尋求一種我們認為有針對性的、有紀律的途徑，以便在財政負責的情況下讓美國以外的患者也能使用 RYTELO。

Our strategy is to work with experienced third parties to help minimize the investment needed outside of the United States, allowing our teams to focus on our top priority of driving our US commercial efforts. We do not plan to commercialize in Europe or any other region outside of the United States independently.

我們的策略是與經驗豐富的第三方合作，幫助最大限度地減少美國以外所需的投資，使我們的團隊能夠專注於推動美國商業努力的首要任務。我們不打算在歐洲或美國以外的任何其他地區獨立進行商業化。

We're also excited about our late-stage clinical development program that could expand imetelstat for use more broadly within hematology and continue to fill unmet needs. IMpactMF is our Phase 3 pivotal trial evaluating imetelstat in relapsed refractory myelofibrosis with an endpoint of overall survival. If we're successful in this trial and imetelstat is approved in this setting, we believe that the opportunity exists to meaningfully expand and potentially double the commercial potential of RYTELO.

我們也對我們的後期臨床開發計劃感到興奮，該計劃可以擴大 imetelstat 在血液學領域的應用範圍，並繼續滿足未滿足的需求。IMpactMF 是我們評估 imetelstat 在復發難治性骨髓纖維化治療的 3 期關鍵試驗，終點為整體存活期。如果我們在這次試驗中取得成功並且 imetelstat 在這種情況下獲得批准，我們相信就有機會顯著擴大 RYTELO 的商業潛力並可能使其翻倍。

Joe will provide an update on enrollment and potential near-term milestones, including the interim analysis that is anticipated in the second half of next year.

喬將提供有關招生情況和潛在近期里程碑的最新信息，包括預計明年下半年進行的中期分析。

Before turning the call over to Jim, I will also mention that our process to identify a permanent Chief Executive Officer is ongoing. Our Board is working with an experienced executive search firm to identify and evaluate candidates with strong commercial leadership in our industry. We expect a decision to be made and announced within the next six months.

在將電話轉給吉姆之前，我還要提到，我們正在尋找一位常任執行長。我們的董事會正在與一家經驗豐富的高階主管搜尋公司合作，以識別和評估我們行業中具有強大商業領導能力的候選人。我們預計將在未來六個月內做出並宣布決定。

With that, I'll hand the call over to Jim to provide a US commercial update.

說完這些，我會把電話交給吉姆，讓他提供美國商業最新消息。

Thanks, Dawn, and good morning, everyone.

謝謝，Dawn，大家早安。

Today I will provide a commercial performance update and highlight key actions we have taken and are continuing to take to drive enhanced launch performance, as well as recent encouraging performance indicators that we are tracking.

今天，我將提供商業績效更新，並強調我們已經採取和正在繼續採取的關鍵行動，以推動提高發布績效，以及我們正在追蹤的最近令人鼓舞的績效指標。

We believe RYTELO is a highly effective novel treatment that fills a significant need in an underserved therapeutic area. We also believe that RYTELO has a strong and differentiated product label, positive NCCN guidelines, and broad US payer coverage. This is why we believe that we can reignite this launch with the plans that we are executing and maximize RYTELO's potential in a market with considerable opportunity.

我們相信 RYTELO 是一種非常有效的新型治療方法，可以滿足醫療服務不足的治療領域的巨大需求。我們還相信，RYTELO 擁有強大且差異化的產品標籤、積極的 NCCN 指南以及廣泛的美國付款人覆蓋範圍。這就是為什麼我們相信，我們可以透過正在執行的計劃重新啟動這項發布，並在充滿機會的市場中最大限度地發揮 RYTELO 的潛力。

On slide 7, we outlined the estimated US total addressable market for RYTELO at approximately 15,400 lower-risk MDS patients based upon the label and NCCN guidelines. To date, most usage has been in the third-line plus setting. Use in later lines often occurs until HCPs gain experience with a new therapeutic agent. There is significant opportunity for RYTELO to expand use in earlier lines of treatment, including first-line ESA ineligible and second-line ESA relapsed refractory patients.

在第 7 張投影片上，我們根據標籤和 NCCN 指南概述了 RYTELO 在美國預計的總目標市場，約 15,400 名低風險 MDS 患者。到目前為止，大多數用途都是在三線以上設定。在 HCP 獲得使用新治療劑的經驗之前，通常會在後期使用。RYTELO 具有巨大的機會擴大其在早期治療中的應用，包括一線 ESA 不符合條件的患者和二線 ESA 復發難治患者。

In Europe, we estimate that the EU4 total addressable market for RYTELO is approximately 80% of the US Later in this call, Joe will provide an update on our ongoing Phase 3 relapsed refractory myelofibrosis clinical trial, IMpactMF, with a planned interim analysis expected in the second half of 2026.

在歐洲，我們估計 RYTELO 在 EU4 的總可尋址市場約為美國的 80%。在本次電話會議的稍後部分，Joe 將提供有關我們正在進行的 3 期復發難治性骨髓纖維化臨床試驗 IMpactMF 的最新情況，併計劃在 2026 年下半年進行中期分析。

Early pre-commercial planning, including market and landscape assessment, is now underway. Our preliminary estimate for the US total addressable market is approximately 10,000 JAK inhibitor relapsed refractory myelofibrosis patients, and the [EU4] total addressable market is approximately 9,000 JAK inhibitor relapsed refractory myelofibrosis patients.

目前正在進行早期商業前期規劃，包括市場和景觀評估。我們對美國總目標市場的初步估計約為 10,000 名 JAK 抑制劑復發難治性骨髓纖維化患者，而 [EU4] 總目標市場約為 9,000 名 JAK 抑制劑復發難治性骨髓纖維化患者。

We will provide commercial planning updates as we approach key IMpactMF clinical and regulatory milestones. Our top corporate priority is the successful commercialization of RYTELO in the US. On slide 8, I will highlight our strategies, plan of action, and thoughtful investments to support this priority. First, we are working to improve RYTELO brand awareness, and we have invested in our team to better reach, inform, and educate healthcare providers, especially community-based HCPs.

當我們接近 IMpactMF 關鍵臨床和監管里程碑時，我們將提供商業規劃更新。我們的首要任務是在美國成功實現 RYTELO 的商業化。在第 8 張投影片上，我將重點介紹我們的策略、行動計畫和周到的投資，以支持這項優先事項。首先，我們正在努力提高 RYTELO 品牌知名度，並且我們已經對我們的團隊進行了投資，以便更好地接觸、告知和教育醫療保健提供者，尤其是社區 HCP。

Our strategy is to increase our brand awareness through greater presence and share of voice within our HCP targets to treat the majority of lower-risk MDS patients. We believe that the sales team is the most effective and efficient way to reach our target HCP audience with an aligned message and one of the most powerful communication forces we can employ to make an impact quickly.

我們的策略是透過在 HCP 目標中提高存在感和話語權來提高我們的品牌知名度，以治療大多數低風險 MDS 患者。我們相信，銷售團隊是我們向目標 HCP 受眾傳達一致訊息的最有效、最高效的方式，也是我們可以採用的最強大的溝通力量之一，可以迅速產生影響力。

We are increasing our customer-facing teams by more than 20%, which is designed to improve our reach and message delivery, especially for higher-decile HCPs who treat the greatest number of RYTELO-eligible lower-risk MDS patients. This expansion includes adding not only additional key account managers, but also oncology clinical educators and a newly created field-based regional marketing team.

我們將面向客戶的團隊規模增加了 20% 以上，旨在提高我們的覆蓋範圍和資訊傳遞能力，特別是針對那些治療最多符合 RYTELO 資格的低風險 MDS 患者的高十分位數 HCP。此次擴張不僅包括增加額外的大客戶經理，還包括增加腫瘤臨床教育者和新成立的基於現場的區域行銷團隊。

Recruiting and hiring is underway. We plan to have the new hires on board and in the field beginning in early Q3 and expect to see their impact later this year. In addition to the field team expansion, we are also pursuing community-based educational and outreach initiatives, such as speaker programs, webinars, and digital campaigns designed to drive broad reach and awareness, especially for lower-decile community HCPs to treat fewer lower-risk MDS patients and may not see a key account manager as often.

招聘和聘用正在進行中。我們計劃在第三季初開始招募新員工並投入工作，並期望在今年稍後看到他們的影響力。除了擴大現場團隊之外，我們還在開展以社區為基礎的教育和推廣活動，例如演講者計劃、網絡研討會和數位宣傳活動，旨在擴大影響力和提高認識，特別是針對低十分位社區的 HCP，他們治療較少的低風險 MDS 患者，而且可能不會經常見到大客戶經理。

Second, we are working to increase HCP prescribing competence through clinical experience and patient success stories. We believe there is an opportunity to reinforce RYTELO's strong therapeutic profile and product differentiation, especially focusing on the second-line post-ESA or ESA-ineligible patients to drive earlier use aligned with our approved label.

其次，我們正在努力透過臨床經驗和患者的成功案例來提高 HCP 的處方能力。我們相信有機會加強 RYTELO 強大的治療特性和產品差異化，特別是專注於二線 ESA 後或 ESA 不合格患者，以推動與我們批准的標籤一致的早期使用。

Our strategy is to increase HCP prescribing competence and clarity through education and strong messages that reinforce RYTELO's product differentiation through the expanded field team, especially targeting our higher volume, lower-risk MDS treaters. We are also enhancing our omnichannel initiatives, including social and digital campaigns, in an effort to expand the reach of our key marketing messages, especially for our lower volume, community based, lower-risk MDS treaters and complement the messaging efforts of our sales teams.

我們的策略是透過教育和強有力的信息來提高 HCP 的處方能力和清晰度，透過擴大現場團隊來強化 RYTELO 的產品差異化，特別是針對我們數量更多、風險更低的 MDS 治療者。我們也正在加強全通路計劃，包括社交和數位行銷活動，努力擴大我們關鍵行銷訊息的覆蓋面，特別是針對治療量較低、以社區為基礎、風險較低的 MDS 治療者，並補充我們銷售團隊的訊息傳遞工作。

Our commercial and medical affairs teams are also addressing and educating HCPs on appropriate cytopenia management to increase HCP prescribing competence. And Joe will highlight the key considerations on cytopenia management and expectations later during his section.

我們的商業和醫療事務團隊也正在向 HCP 介紹和培訓適當的血球減少症管理，以提高 HCP 的處方能力。喬稍後將在他自己的部分中重點介紹血球減少症管理和預期的關鍵考慮因素。

Third, we are working to generate stronger KOL support and advocacy across the US. We believe that increased KOL advocacy is essential to building broader support and use of RYTELO given the limited number of US clinical trial investigators and patients who participated in IMerge.

第三，我們正在努力在美國各地爭取更強有力的KOL支持和倡議。我們認為，鑑於參與 IMerge 的美國臨床試驗研究人員和患者數量有限，增加 KOL 宣傳對於獲得更廣泛的支持和使用 RYTELO 至關重要。

Our strategy is to strengthen US KOL advocacy through education and engagement supporting our launch success, and we have made investments to do so. To support the commercial team's engagement with KOL, we have further expanded our commercial team headcount, creating a new field-based regional marketing team. Their responsibilities are to cultivate and develop stronger KOL relationships in support of advancing patient care in lower-risk MDS. The regional marketing team identifies opportunities and data needs to further support product differentiation with KOL input and validation.

我們的策略是透過教育和參與來加強美國​​ KOL 宣傳，以支持我們的發布成功，並且我們已經為此進行了投資。為了支持商業團隊與KOL的互動，我們進一步擴大了商業團隊的人數，並創建了新的基於現場的區域行銷團隊。他們的職責是培養和發展更強大的 KOL 關係，以支持推動低風險 MDS 的病患照護。區域行銷團隊透過 KOL 的輸入和驗證來識別機會和數據需求，以進一步支援產品差異化。

Based on these opportunities and needs, the clinical and medical affairs team independently prioritizes data generation opportunities to enhance RYTELO's clinical share of voice with increased publications and presentations at congresses. The regional marketing team will work with top KOLs in peer-to-peer educational initiatives like speaker programs, executive engagement, and community-focused educational initiatives. We are excited about the potential of this newly created team to strengthen our relationship with the top KOL.

根據這些機會和需求，臨床和醫療事務團隊獨立確定資料產生機會的優先順序，以透過增加出版物和在會議上的簡報來增強 RYTELO 在臨床上的聲音份額。區域行銷團隊將與頂級 KOL 合作進行點對點教育計劃，例如演講者計劃、高管參與和以社區為中心的教育計劃。我們對這個新成立的團隊加強我們與頂級 KOL 的關係的潛力感到非常興奮。

Turning to slide 9, we have refined and continue to refine our account and HCP targeting, which we believe will allow us to reach physicians treating the majority of lower-risk MDS patients. We estimate that approximately 6,300 HCPs currently treat approximately 80% of lower-risk MDS patients in the United States.

轉到投影片 9，我們已經完善並將繼續完善我們的帳戶和 HCP 定位，我們相信這將使我們能夠接觸到治療大多數低風險 MDS 患者的醫生。我們估計，目前約有 6,300 名 HCP 治療美國約 80% 的低風險 MDS 患者。

We further estimate that approximately 1,300 HCPs treat approximately 50% of the currently diagnosed lower-risk MDS patients. These data provide good insights into where RYTELO-eligible patients are being treated, and these HCPs are our commercial focus for personal and non-personal promotional efforts. Our refined targeting effort is designed to help us effectively reach, engage, and educate HCPs treating the majority of currently diagnosed RYTELO-eligible lower-risk MDS patients.

我們進一步估計，大約 1,300 名 HCP 治療了目前確診的低風險 MDS 患者的約 50%。這些數據很好地說明了符合 RYTELO 條件的患者在哪裡接受治療，這些 HCP 是我們進行個人和非個人推廣活動的商業重點。我們精心製定的定位工作旨在幫助我們有效地接觸、吸引和教育治療大多數目前診斷為符合 RYTELO 資格的低風險 MDS 患者的 HCP。

Turning to slide 10, we believe these recently implemented and ongoing commercial actions will drive increased product demand over time. While early, we are pleased to see modest improvements in several leading commercial performance indicators.

轉到第 10 張投影片，我們相信這些最近實施和正在進行的商業行動將隨著時間的推移推動產品需求的成長。雖然還處於早期階段，但我們很高興看到幾個領先的商業績效指標略有改善。

As of April 2025, approximately 900 sites of care have utilized RYTELO. This is an increase of almost 300 new sites since the end of Q4. Of the accounts that previously ordered, approximately two-thirds have reordered in Q1.

截至 2025 年 4 月，約有 900 個護理站點使用了 RYTELO。自第四季末以來，新站點數量增加了近 300 個。在先前訂購的帳戶中，大約三分之二已在第一季重新訂購。

Demand grew approximately 10% in the current four-week period ending April '25, compared to the prior four-week period. This represents the highest month-over-month growth since October 2024. The rolling three-month market claims data as of February 2025 estimates that approximately 25% of RYTELO new patient starts were in the first and second lines.

與前四周相比，截至 2025 年 4 月的當前四周內需求增加了約 10%。這是自 2024 年 10 月以來最高的月成長率。截至 2025 年 2 月的三個月滾動市場索賠數據估計，RYTELO 新患者中約有 25% 來自第一線和第二線。

We expect to see an increase in second-line use as HCPs gain more experience with RYTELO and become more comfortable prescribing it in earlier settings. Our recent market research evaluating intention-to-treat suggests physicians intend to use RYTELO in earlier lines of therapy.

隨著 HCP 對 RYTELO 的使用經驗越來越豐富，並且在早期環境中更習慣於開立該藥物的處方，我們預計二線使用量將會增加。我們最近進行的意向治療市場調查表明，醫生打算在早期治療中使用 RYTELO。

Payor access continues to strengthen with approximately 85% of US covered lives now under favorable RYTELO medical coverage policies that are consistent with the FDA label and our NCCN guidelines. I want to acknowledge the cross-functional team and especially the sales team who are executing the plan to deliver on these leading performance indicators and demonstrating strong patient centricity.

付款人的存取權持續加強，目前約 85% 的美國受保人享有符合 FDA 標籤和我們的 NCCN 指南的優惠 RYTELO 醫療保險政策。我要感謝跨職能團隊，特別是銷售團隊，他們正在執行計劃，實現這些領先的績效指標，並表現出強烈的以患者為中心的精神。

Turning to the EU, we outlined key considerations in our launch planning on slide 11. We have assembled a small experienced team to focus on EU4 launch preparation. We anticipate commercialization in select EU4 countries starting in 2026 pending favorable reimbursement and completion of critical launch activities. Commercial success in ex-US markets is dependent on strong reimbursement and favorable pricing. We are engaging established third-party partners across commercial, market access, medical affairs, ATOR, and distribution to prepare for successful commercialization.

談到歐盟，我們在第 11 張幻燈片中概述了發布計劃中的關鍵考慮因素。我們組建了一支經驗豐富的小型團隊，專注於 EU4 的發布準備工作。我們預計，在獲得有利的補償和完成關鍵的發射活動後，將從 2026 年開始在部分 EU4 國家實現商業化。美國以外市場的商業成功取決於強大的報銷和優惠的定價。我們正在與商業、市場准入、醫療事務、ATOR 和分銷領域的成熟第三方合作夥伴合作，為成功的商業化做好準備。

We also expect to maintain financial discipline in investing for the EU4 launch with further expansion pending strong reimbursement. We will provide future EU launch planning updates as we progress towards commercialization. In summary, we have implemented and continue to implement actions specifically designed to enhance US sales performance.

我們也希望在投資 EU4 的發佈時保持財務紀律，並在獲得豐厚回報後進一步擴張。隨著我們逐步實現商業化，我們將提供未來歐盟發布計畫的更新。總而言之，我們已經實施並將繼續實施專門為提高美國銷售業績而設計的行動。

We remain confident in the long-term potential of RYTELO as a differentiated therapeutic for eligible patients with lower risk MDS. We are aligned on the opportunity and responsibility in front of us, and we are all in on driving success of RYTELO.

我們仍然對 RYTELO 作為適合低風險 MDS 患者的差異化治療方法的長期潛力充滿信心。我們對眼前的機會和責任有著一致的認識，我們全力以赴推動 RYTELO 的成功。

I will now turn the call over to Joe Eid who will provide medical affairs and clinical development updates.

現在我將電話轉給 Joe Eid，他將提供醫療事務和臨床開發的最新資訊。

Thank you, Jim. I'd like to start by sharing several recent accomplishments from the medical affairs organization.

謝謝你，吉姆。首先，我想分享一下醫療事務組織最近的幾項成就。

Since our last earnings goal, we've implemented steps to further support community awareness of RYTELO, develop HCP confidence in how and where to prescribe, and generate KOL advocacy within the lower risk MDS HCP community. I'm happy to share that we are executing on our plan. We are growing our medical science liaison footprint to reach more accounts by aligning their territorial coverage with the anticipated expansion of our commercial field team. This effort should help us achieve more streamlined and coordinated account management.

自上次實現盈利目標以來，我們已採取措施進一步支持社區對 RYTELO 的認識，培養 HCP 對如何以及在何處開處方的信心，並在低風險 MDS HCP 社區中產生 KOL 宣傳。我很高興地告訴大家，我們正在執行我們的計劃。我們正在擴大我們的醫學科學聯絡範圍，以便透過將其地域覆蓋範圍與我們的商業現場團隊的預期擴張相結合來接觸更多的客戶。這項努力應該有助於我們實現更精簡和協調的帳戶管理。

Our field team interacts with HCPs frequently and is aligned with our corporate strategy to reach and educate the lower risk MDS prescriber community and key opinion leaders. We've expanded the team with payer-focused MSLs and bolstered leadership in both publication planning and HE award.

我們的現場團隊經常與 HCP 互動，並與我們的公司策略保持一致，以接觸和教育低風險 MDS 處方者社群和關鍵意見領袖。我們擴大了以付款人為中心的 MSL 團隊，並加強了出版規劃和 HE 獎項的領導力。

In fact, we are in the process of doubling the size of our overall medical affairs team since our last earnings goal. We have been focused on increasing executive engagement with key institutions and thought leaders to share our data, discuss research areas of interest, and collect insights to inform our strategy.

事實上，自上次設定獲利目標以來，我們正在將整體醫療事務團隊的規模擴大一倍。我們一直致力於加強與主要機構和思想領袖的高層互動，以分享我們的數據、討論感興趣的研究領域並收集見解來為我們的策略提供資訊。

We are pleased with the positive feedback we have been hearing in these meetings. Key opinion leaders are interested in RYTELO's unique mechanism of action and learning more about our data that suggests the potential for disease modification. As Jim noted, we are also focused on increasing HCP awareness of RYTELO, particularly in the community setting and in centers that did not participate in our phase three pivotal trial, which enrolled the vast majority of patients outside of the United States.

我們很高興聽到這些會議中的正面回饋。關鍵意見領袖對 RYTELO 獨特的作用機制很感興趣，並希望了解更多表明其具有改變疾病潛力的數據。正如吉姆所指出的，我們也致力於提高 HCP 對 RYTELO 的認識，特別是在社區環境中以及未參與我們第三階段關鍵試驗的中心，該試驗招募了絕大多數美國以外的患者。

We are increasing our efforts to educate and inform the US prescriber community and key thought leaders. We are also pleased with the positive feedback received from many physicians who have shared their positive experience with RYTELO's efficacy, especially in those hard-to-treat lower risk MDS patients who are not served well with other approved therapies.

我們正在加強教育和告知美國處方者社區和主要思想領袖。我們也很高興收到許多醫生的正面回饋，他們分享了對 RYTELO 療效的正面體驗，特別是對於那些難以治療的低風險 MDS 患者，他們使用其他核准療法效果不佳。

We are also pleased to hear their feedback regarding their experience with RYTELO's safety profile, which has generally been that RYTELO has a manageable safety profile, including the management of cytopenia, which are considered on target or unsurprising, given the drug's unique mechanism of action. In addition, we have received positive feedback of patients' experiences regarding fatigue, where other approved therapies can fall short.

我們也很高興聽到他們關於 RYTELO 安全性體驗的反饋，總體而言，RYTELO 具有可控的安全性，包括對血球減少症的管理，考慮到該藥物獨特的作用機制，這些反饋被認為是符合目標或不足為奇的。此外，我們收到了患者關於疲勞體驗的正面回饋，而其他核准的療法可能存在不足。

Our clinical experience with imetelstat aligns with what we observed in the preclinical data. An exploratory analysis of the phase three IMerge data showed that the exposure to imetelstat correlated both qualitatively and quantitatively with reduction in mutation burden. In other words, we observed a decrease in the number and type of mutations. This exploratory analysis showed that long and durable responders tended to have a strong correlation with mutation burden reduction. We believe that these correlations illustrate the unique mechanism of action of imetelstat.

我們對 imetelstat 的臨床經驗與我們在臨床前數據中觀察到的情況一致。對第三階段 IMerge 數據的探索性分析表明，imetelstat 的暴露與突變負擔的減少在質量和數量上均相關。換句話說，我們觀察到突變的數量和類型的減少。這項探索性分析表明，長期持久的反應者往往與突變負擔的減少有強烈的相關性。我們相信這些相關性說明了imetelstat獨特的作用機制。

Looking ahead, we are excited about the upcoming American Society of Clinical Oncology and European Hematology Association annual meetings this June. We have a robust plan in place at these key medical conferences to engage with many of our investigators and thought leaders, and we plan on holding strategic advisory board meetings to discuss our plans and to inform our strategies. We look forward to reconnecting with many of our stakeholders in Chicago and Milan next month.

展望未來，我們對今年 6 月即將舉行的美國臨床腫瘤學會和歐洲血液學會年會感到興奮。我們在這些重要的醫學會議上製定了強有力的計劃，與我們的許多研究人員和思想領袖進行交流，並且我們計劃召開戰略諮詢委員會會議來討論我們的計劃並告知我們的戰略。我們期待下個月與芝加哥和米蘭的許多利益相關者重新建立聯繫。

Additionally, to build on the momentum from these conferences, we plan to continue actively sharing our progress at key venues and in key journals in order to further increase support from the medical and scientific communities. We continue to receive imetelstat research interests from investigators, and given its unique mechanism of action, there is eagerness to evaluate imetelstat in new settings as well as new indications.

此外，為了藉助這些會議的勢頭，我們計劃繼續在主要會場和主要期刊上積極分享我們的進展，以進一步增加醫學界和科學界的支持。我們不斷收到研究人員的 imetelstat 研究興趣，並且鑑於其獨特的作用機制，人們渴望在新的環境和新的適應症中評估 imetelstat。

As Don and Jim mentioned, our focus and top priority remains US commercialization, and we intend to be disciplined in how we deploy our resources. In the EU, we are working closely with the commercial team, and we intend to stand up and access programs to provide RYTELO to eligible patients with low-risk and intermediate one MDS. I'd also like to provide an update on our IMpactMF Phase 3 trial in relapsed refractory myelofibrosis, and discuss why we're excited about expanding imetelstat in this indication.

正如唐和吉姆所提到的，我們的重點和首要任務仍然是美國的商業化，我們打算嚴格控制資源的部署。在歐盟，我們正在與商業團隊密切合作，並打算啟動和訪問計劃，為符合條件的低風險和中度 MDS 患者提供 RYTELO。我還想提供我們在復發難治性骨髓纖維化中的 IMpactMF 3 期試驗的最新進展，並討論為什麼我們對擴大 imetelstat 在此適應症中的應用感到興奮。

As you know, we based the IMpactMF Phase 3 trial on our single-arm Phase 2 trial in the same JAK inhibitor relapsed refractory myelofibrosis population. In that trial, we saw a strong signal regarding prolonged survival and decreased bone marrow fibrosis after treatment, suggesting the potential for disease modification.

如您所知，我們根據在同一 JAK 抑制劑復發難治性骨髓纖維化人群中進行的單臂 2 期試驗開展了 IMpactMF 3 期試驗。在該試驗中，我們看到了治療後生存期延長和骨髓纖維化減少的強烈訊號，這表明有改變疾病的潛力。

First, we observed a prolongation of survival of almost threefold when compared with a historical cohort. Second, we observed decreased bone marrow fibrosis or complete reversal after treatment with imetelstat. These significant observations gave us confidence in pursuing the registrational study in relapsed refractory myelofibrosis. Our confidence also stems from the unique mechanism of action of imetelstat.

首先，與歷史隊列相比，我們觀察到生存期延長了近三倍。其次，我們觀察到使用imetelstat治療後骨髓纖維化減少或完全逆轉。這些重要的觀察結果使我們對進行復發難治性骨髓纖維化的註冊研究充滿信心。我們的信心也源自於imetelstat獨特的作用機制。

Telomeres are repetitive [5-3] DNA sequences at the end of chromosomes and serve as protective caps that can help maintain the stability and integrity of chief chromosomes. Telomerase is an enzyme that maintains telomere length in rapidly dividing cells. Telomerase is upregulated in more than 90% of cancers, including myelodysplastic syndrome, NMF, and leads to cells dividing uncontrollably without reaching the Hayflick limit, thereby evading apoptosis.

端粒是染色體末端重複的 [5-3] DNA 序列，起到保護帽的作用，有助於維持主染色體的穩定性和完整性。端粒酶是一種在快速分裂的細胞中維持端粒長度的酵素。端粒酶在超過 90% 的癌症中上調，包括骨髓增生異常綜合症 (NMF)，並導致細胞分裂失控而無法達到海弗利克極限，從而逃避細胞凋亡。

RYTALO is the first and only telomerase inhibitor approved by FDA for certain lower-risk MDS patients and is being evaluated in relapsed refractory myelofibrosis in a Phase 3 ongoing trial. We are very encouraged with the continued interest in the IMpactMF 3 trial, which is currently approximately 85% enrolled and expected to be on track to complete enrollment. Based on current assumptions of death events, we expect the interim analysis to read out in the second half of 2026.

RYTALO 是 FDA 核准用於治療某些低風險 MDS 患者的首個也是唯一一個端粒酶抑制劑，目前正在進行 3 期試驗以評估其對復發難治性骨髓纖維化的作用。我們對 IMpactMF 3 試驗持續受到關注感到非常鼓舞，目前該試驗的入組率約為 85%，預計將順利完成入組。根據目前對死亡事件的假設，我們預計中期分析結果將於 2026 年下半年公佈。

It is important to remember that the OS primary endpoint is event-driven and the timeline for interim and final analyses are tied to the number of death events. The IMpactMF 3 trial is designed with a 2:1 randomization, and the number of patients on the imetelstat arm are double the number of patients on the best available therapy arm.

重要的是要記住，OS 主要終點是事件驅動的，中期和最終分析的時間表與死亡事件的數量相關。IMpactMF 3 試驗採用 2:1 隨機化設計，imetelstat 組的患者人數是最佳可用治療組患者人數的兩倍。

In addition to this Phase 3 trial, we also have the IMproveMF Phase 1 trial, which is a frontline myelofibrosis study of imetelstat in combination with JAK inhibitor. This trial completed the dose escalation stage. We were encouraged to be able to dose ruxolitinib and imetelstat at the maximum intended doses of each without observed NPD. We also observed fewer cytopenias than seen in the IMerge trial.

除了這項 3 期試驗外，我們還有 IMproveMF 1 期試驗，這是一項 imetelstat 與 JAK 抑制劑合併治療一線骨髓纖維化的研究。本次試驗完成了劑量遞增階段。我們受到鼓舞，能夠以各自的最大預期劑量對魯索利替尼和伊米特司進行給藥，而不會觀察到 NPD。我們也觀察到比 IMerge 試驗中更少的血球減少症。

The second stage of the study is enrolling now, and we are seeing excitement from the investigator community for this combination and its potential for patients with MS. This is a great opportunity for patients with unmet need and for geo-uncontinued growth. We believe that this is an important opportunity to investigate whether imetelstat might be able to benefit additional patients with unmet need.

研究的第二階段目前正在招募患者，我們看到研究人員對這種組合及其對 MS 患者的潛力感到興奮。對於尚未滿足需求的患者和地理未持續成長的患者來說，這是一個很好的機會。我們相信，這是一個重要的機會來研究 imetelstat 是否能夠使更多未滿足需求的患者受益。

I'll now pass the call to Michelle to review our Q1 financial results.

我現在將電話轉給米歇爾來審查我們的第一季財務表現。

Thank you, Joe, and good morning, everyone. For detailed results from the quarter, please refer to the press release we issued this morning, which is available on our website.

謝謝你，喬，大家早安。有關本季的詳細業績，請參閱我們今天上午發布的新聞稿，該新聞稿可在我們的網站上查閱。

As of March 31, 2025, we had approximately $457.5 million in cash, cash equivalents, restricted cash, and marketable securities, compared to $502.9 million as of December 31, 2024. Total net product revenue and total net revenue for the three months ending March 31, 2025 were $39.4 million. There were no products or net revenues in the first quarter of last year since RYTELO was approved by the FDA in June of 2024.

截至 2025 年 3 月 31 日，我們擁有約 4.575 億美元的現金、現金等價物、受限現金和有價證券，而截至 2024 年 12 月 31 日為 5.029 億美元。截至 2025 年 3 月 31 日的三個月的總淨產品收入和總淨收入為 3,940 萬美元。自 2024 年 6 月 RYTELO 獲得 FDA 批准以來，去年第一季沒有任何產品或淨收入。

As Dawn mentioned, Q1 RYTELO net revenues were down approximately $8 million from Q4, while demand in the 13-week period through the week ending March 28 was relatively flat versus the prior 13 weeks. The lower quarter-over-quarter net revenue is due to the inventory drawdown among our distributors from Q4 into Q1.

正如 Dawn 所提到的，RYTELO 第一季淨收入較第四季下降約 800 萬美元，而截至 3 月 28 日當週的 13 週內的需求與前 13 週相比基本持平。季度淨收入較上一季下降的原因是我們的經銷商從第四季到第一季的庫存減少。

As a reminder, revenue recognition occurs when specialty pharmacies, specialty distributors, and GPOs receive RYTELO. Growth to net was similar from Q4 to Q1 and did not significantly contribute to the quarter-over-quarter net revenue decline.

提醒一下，當專業藥局、專業經銷商和 GPO 收到 RYTELO 時就會確認收入。第四季的淨收入成長與第一季相似，並未對季度環比淨收入下降造成顯著影響。

As Jim mentioned, we are encouraged by sales trends since the end of Q1, as we had the highest month-over-month demand growth as of April '25 since last October, representing a 10% increase in the current four-week period compared to the prior four weeks. Research and development expenses for the three months ending March 31, 2025 were $15.1 million compared to $29.4 million for the same period in 2024.

正如吉姆所提到的，我們對第一季末以來的銷售趨勢感到鼓舞，因為截至 2025 年 4 月，我們的月度需求成長率是自去年 10 月以來最高的，與前四周相比，目前四周增長了 10%。截至 2025 年 3 月 31 日的三個月的研發費用為 1,510 萬美元，而 2024 年同期為 2,940 萬美元。

The decrease was primarily due to lower clinical trial costs associated with the wind-down activity in our Phase 3 IMerge MDS study at the FDA approval of RYTELO in 2024, as well as manufacturing and quality costs that were capitalized in the current period now that RYTELO has been approved versus being expensed in the prior year period prior to commercialization.

下降的主要原因是，在 2024 年 FDA 批准 RYTELO 時，我們第 3 階段 IMerge MDS 研究中逐漸減少的活動相關的臨床試驗成本較低，以及製造和質量成本在 RYTELO 獲得批准後在本期資本化，而不是在商業化之前的上一年期間費用化。

Selling, general, and administrative expenses for the three months ending March 31, 2025 were $40 million compared to $27.1 million for the same period last year. The increase was primarily due to higher personnel expenses related to additional headcount to support the commercialization of RYTELO in the US.

截至 2025 年 3 月 31 日的三個月的銷售、一般及管理費用為 4,000 萬美元，而去年同期為 2,710 萬美元。成長的主要原因是與支持 RYTELO 在美國商業化而增加員工相關的人事費用增加。

For fiscal year 2025, we still expect our total operating expenses to be in the range of approximately $270 million to $285 million. This includes expenses associated with our continued investment in our RYTELO commercialization strategy, investment in commercial supply redundancies, post-marketing commitments, as well as initial preparations to launch RYTELO in selected EU countries in 2026, including the [HTA] evaluation process. We will be able to provide additional details as we approach the planned launch next year, but the initial work associated with launch preparation in the EU is budgeted into our long-term plans.

對於 2025 財年，我們仍預計總營運費用將在約 2.7 億美元至 2.85 億美元之間。這包括與我們對 RYTELO 商業化策略的持續投資、對商業供應冗餘的投資、上市後承諾以及 2026 年在部分歐盟國家推出 RYTELO 的初步準備（包括 [HTA] 評估過程）相關的費用。隨著明年計劃發射的臨近，我們將能夠提供更多細節，但與歐盟發射準備相關的初步工作已納入我們的長期計劃。

Overall, we are confident that GRON remains in a strong financial position as we continue to integrate commercial strategy refinements outlined by Dawn and Jim, as well as monitor our sales trajectory, we will evaluate our timeline for achieving profitability. As a reminder, we have access to additional funding under our debt agreement with Pharmakon if needed.

總體而言，我們相信，隨著我們繼續整合 Dawn 和 Jim 概述的商業策略改進，以及監控我們的銷售軌跡，GRON 仍將保持強勁的財務狀況，我們將評估獲利的時間表。提醒一下，如果需要，我們可以根據與 Pharmakon 簽訂的債務協議獲得額外資金。

With that, I'll turn it back to Dawn.

說完這些，我就把它交還給 Dawn。

Thank you, Michelle, and thank you all again for joining us today. We believe RYTELO is a differentiated product for the treatment of certain patients with lower-risk MDS, a disease with high unmet need. The first quarter sales were modest by our expectations, and we don't believe this reflects the product's true commercial potential.

謝謝你，米歇爾，再次感謝大家今天的到來。我們相信 RYTELO 是一種差異化產品，可用於治療某些低風險 MDS 患者，而 MDS 是一種尚未滿足的疾病。根據我們的預期，第一季的銷售額並不高，我們認為這並不能反映該產品的真正商業潛力。

I want to reiterate, our top priority remains US commercialization and making RYTELO part of the standard of care for eligible lower-risk MDS patients. The Geron team is energized by this responsibility, and we believe that we've made and continue to make the appropriate investments to support the success of our US commercial business.

我想重申，我們的首要任務仍然是在美國實現商業化，並使 RYTELO 成為符合條件的低風險 MDS 患者的標準治療的一部分。Geron 團隊對這項責任充滿活力，我們相信我們已經做出並將繼續做出適當的投資來支持我們美國商業業務的成功。

While it's still early, we're beginning to see a few promising performance indicators and are ready to make diligent and swift adjustments as needed to further improve upon our commercial execution. EU commercialization and access to Imitelstat are significant Geron priorities. We are carefully balancing our desire to make this important medicine available to lower-risk MDS patients in the EU with thoughtful and disciplined resourcing, allowing our team to focus on RYTELO's success here in the United States.

雖然還處於早期階段，但我們已經開始看到一些有希望的績效指標，並準備根據需要進行勤勉和迅速的調整，以進一步改善我們的商業執行。歐盟對 Imitelstat 的商業化和取得是 Geron 的重要優先事項。我們正在謹慎地平衡我們的願望，讓歐盟的低風險 MDS 患者能夠獲得這種重要藥物，並透過周到而嚴謹的資源配置，讓我們的團隊專注於 RYTELO 在美國取得成功。

And lastly, we're excited as we look towards the future. Our pivotal Phase 3 trial evaluating imetelstat in relapsed refractory MF patients with an overall survival endpoint, if successful and approved in this setting, could potentially double the commercial opportunity of RYTELO. We expect that the interim data analysis could occur as soon as the second half of 2026.

最後，我們對未來充滿期待。我們的關鍵性 3 期試驗評估了 imetelstat 對複發性難治性 MF 患者的整體生存終點，如果在該環境下取得成功並獲得批准，則可能使 RYTELO 的商業機會翻倍。我們預計中期數據分析最快可能在 2026 年下半年進行。

We look forward to keeping you informed of our progress across all of these priorities and will now open the line for questions. Operator?

我們期待向您通報我們在所有這些優先事項上取得的進展，現在我們將開放提問熱線。操作員？

(Operator Instructions) Tara Bancroft, TD Cowen.

（操作員指示）Tara Bancroft，TD Cowen。

Hi. Good morning. So I'm hoping just with the inventory impacts essentially behind you, demand is improving in recent weeks, and the increased number of commercial reps that you have out in the field and growing through Q3, can you help us understand how you're thinking about Q2 expectations and just the expected cadence for the year as to when these efforts can potentially lead to inflection in your view?

你好。早安.因此，我希望，隨著庫存影響基本消失，最近幾週需求有所改善，以及您在實地擁有的商業代表數量在第三季度不斷增加，您能否幫助我們了解您對第二季度預期的看法以及今年的預期節奏，即這些努力何時可能在您看來帶來轉折？

Hi, Tara. It's Dawn Bir. Thank you so much for your question. Yes, we're excited about the future and the plans that we've put in place. So I'll allow Jim to address your question here.

你好，塔拉。我是 Dawn Bir。非常感謝您的提問。是的，我們對未來和我們所製定的計劃感到興奮。因此我讓吉姆在這裡回答你的問題。

Great. Hi, Tara. Good morning. In terms of Q1, thanks for acknowledging that inventory played a factor and explains the difference between revenues and underlying demand, which grew at about 1%, Q1 over Q4. A lot of the changes that we are making and will make will start to have an impact now and going forward.

偉大的。你好，塔拉。早安.就第一季而言，感謝您承認庫存是一個因素，並解釋了收入和潛在需求之間的差異，第一季比第四季度增長了約 1%。我們正在進行和將要進行的許多變革將對現在和未來產生影響。

Your specific question around the reps, we're adding the reps. We anticipate they will be in the field beginning in Q3, so we'll see their impact later this year. A couple of the promising data points that we acknowledged on the call were the increase of approximately 300 new ordering sites, Q1 over Q4, the 10% increasing growth of April over March.

您關於代表的具體問題，我們正在添加代表。我們預計他們將從第三季開始投入使用，因此我們將在今年晚些時候看到他們的影響。我們在電話會議上承認的幾個有希望的數據點是，第一季比第四季增加了約 300 個新的訂購站點，4 月的成長率比 3 月增加了 10%。

So what we anticipate is continued momentum building into Q2 and sustaining throughout the year through 2025.

因此，我們預計這一勢頭將在第二季度繼續增強，並持續到 2025 年全年。

Greg Harrison, Scotiabank.

加拿大豐業銀行的格雷格·哈里森。

This is [Teresa Vitale] on for Greg Harrison. Thanks for taking our question. I was curious if you can comment on your commercial efforts to drive the assessment of efficacy for patients on this Patercept to an earlier stage in order to help promote switching to RYTELO and maybe what are KOL citing as their reasoning behind any hesitation in switching patients from standard of care and prescribing RYTELO in earlier lines of therapy?

我是 [Teresa Vitale]，為 Greg Harrison 報道。感謝您回答我們的問題。我很好奇，您是否可以評論一下您在商業上所做的努力，即推動對 Patercept 患者的療效評估進入早期階段，以幫助促進患者轉向 RYTELO，也許 KOL 所引用的理由是，他們為什麼猶豫讓患者放棄標準治療，轉而使用 RYTELO 作為早期治療方案？

Thank you. Teresa, good morning, and thank you for your question. I think maybe to address your question, we'll start first with Jim, but I think Joe could provide a great perspective from the medical affairs point of view. So I'll let Jim kick this off.

謝謝。特蕾莎，早上好，謝謝你的提問。我想也許為了回答你的問題，我們先從吉姆開始，但我認為喬可以從醫療事務的角度提供一個很好的觀點。所以我讓吉姆開始吧。

Sure. Let's talk first about perceptions, behaviors, and results. We do something called ATU market research, awareness trial utilization, and it all begins with awareness. What we see in the market research is that when physicians are aware of RYTELO's product profile, they view it favorably compared to those that don't understand it, and that holds for both efficacy as well as cytopenia management. In our most recent ATU, we saw a nice shift of cytopenia management, especially among those that have used RYTELO being viewed as much more manageable than those that haven't used it.

當然。我們先來談談看法、行為和結果。我們做了一些稱為 ATU 市場研究、意識試驗利用的事情，而這一切都始於意識。我們在市場調查中發現，當醫生了解 RYTELO 的產品概況時，他們會比不了解該產品概況的醫生對其持更積極的看法，這對於療效和血球減少症管理均是如此。在我們最近的 ATU 中，我們看到了血球減少症管理的良好轉變，尤其是使用過 RYTELO 的人比那些沒有使用過 RYTELO 的人更容易管理。

In terms of efficacy, one of the nice data points that we saw in the most recent market research is that the perceptions around second-line RS negative has definitely shifted and increased as a source of product differentiation. The reason why I bring this up is first to acknowledge the messages delivered by the field course are resonating with the physicians. We expect to see those perceptions to translate into changes in behavior.

就療效而言，我們在最近的市場調查中看到的一個很好的數據點是，圍繞二線 RS 陰性的看法肯定已經發生了轉變，並且作為產品差異化的來源而有所增加。我之所以提起這件事，首先是為了承認實地課程傳遞的訊息引起了醫生們的共鳴。我們希望看到這些看法轉化為行為的改變。

The data point that I shared on the call, which is very positive, is that in the most recent data, we had about 20% utilization in first and second line, which is an increase over the previous results. These are all leading indicators for sustained growth. I want to, again, acknowledge our customer-facing teams, both the CAMs as well as the oncology clinical educators, for delivering the message because, as we highlighted earlier, when the message is delivered, there is impact.

我在電話中分享的數據點非常積極，那就是在最新數據中，我們第一線和第二線的利用率約為 20%，這比之前的結果有所增加。這些都是持續成長的領先指標。我想再次感謝我們面向客戶的團隊，包括 CAM 和腫瘤學臨床教育者，感謝他們傳遞了訊息，因為正如我們之前強調的那樣，訊息一旦傳遞，就會產生影響。

Maybe to complement Jim's answer, you specifically asked about the post-luspatercept. Obviously, as we know, in the IMerge study, there was a limited number of patients who had received luspatercept, given that it was in the early days of its approval. However, we did have subsequent trials that did include patients who had received luspatercept. We presented data at ASH last December that showed the activity of imetelstat, post-CSA, post-luspa, heavy transfusion burden, mutation burden.

也許是為了補充吉姆的回答，你特別詢問了服用 luspatercept 後的情況。顯然，正如我們所知，在 IMerge 研究中，接受 luspatercept 治療的患者數量有限，因為該藥物仍處於批准初期。然而，我們確實進行了後續試驗，其中確實包括接受過 luspatercept 治療的患者。我們去年 12 月在 ASH 上展示了數據，顯示了 imetelstat 的活性、CSA 後、luspa 後、重度輸血負擔、突變負擔。

All these patients responded in a similar manner. There will be, obviously, more patients from the real-world data that we are collecting providing additional information about that specific topic.

所有這些患者的反應都相似。顯然，我們收集的真實世界數據中將會有更多患者提供有關該特定主題的更多資訊。

In terms of hesitancy, as Jim has mentioned and I will reemphasize, physicians who are using Imitalstat have experienced the positive benefit of this on their patients. That is encouraging. The efficacy is somewhat unparalleled in this space where we are seeing robust hemoglobin rises and patients' quality of life improving.

至於猶豫，正如吉姆所提到的，我將再次強調，使用 Imitalstat 的醫生已經感受到了它對他們的患者的積極益處。這令人鼓舞。其療效在這一領域是無與倫比的，我們看到血紅蛋白強勁上升，患者的生活品質得到改善。

Peter Lawson, Barclays.

巴克萊銀行的彼得·勞森。

Jim, maybe you could walk through the inventory issue. Was that due to a distributor stocking in 4Q? The dynamics there that we should be thinking about as the inventory has been burned through. Do you think that is corrected?

吉姆，也許你可以討論一下庫存問題。這是因為第四季經銷商囤貨嗎？由於庫存已被消耗殆盡，我們應該考慮那裡的動態。您認為這是否正確？

Thanks, Peter. First, I want to acknowledge that there are several factors that contributed to the higher inventory first. Prior to the holidays, we were on a growth trend. Many of our SPs and STs were using history to project the future going forward. As the trend started to flatten, the inventory increased. The second factor, as we talked about before, was some level of seasonality that affected our products as well as other products in our category.

謝謝，彼得。首先，我想承認有幾個因素導致了庫存增加。假期前，我們處於成長趨勢。我們的許多 SP 和 ST 都在利用歷史來預測未來。隨著趨勢開始趨於平緩，庫存增加。第二個因素，正如我們之前談到的，是某種程度的季節性，它影響了我們的產品以及我們類別中的其他產品。

The third thing is perhaps there was some anticipation of pricing or reimbursement issues, which is not specific to RYTELO, but affects all buy and build products. While the inventory was probably at the higher end of the range towards the end of the year, we did start to draw down that inventory. That explains the difference between the drop in net revenues, yet the 1% increase in demand.

第三件事可能是對定價或報銷問題有一些預期，這並非 RYTELO 獨有，而是影響所有購買和建立產品。雖然到年底庫存可能處於較高水平，但我們確實開始減少庫存。這解釋了淨收入下降而需求增加 1% 之間的差異。

Thanks for the question, Peter.

謝謝你的提問，彼得。

Great. Do you think that stabilized issues with slow and unexpected pull-through and stocking? Do you think that is in a good spot for 2Q?

偉大的。您是否認為這可以穩定緩慢且意外的拉動和庫存問題？您認為這對第二季來說是一個好時機嗎？

We do, Peter. Thanks. Yes.

是的，彼得。謝謝。是的。

Great. Okay. Thank you. You mentioned 1,300 high-priority HCPs. How many are currently covered by the field team? How frequently do they call? Where do you want that metric to be in the second half of this year?

偉大的。好的。謝謝。您提到了 1,300 名高優先級 HCP。目前實地團隊涵蓋了多少人？他們多久打一次電話？您希望今年下半年該指標達到什麼水準？

Peter, we're not going to give the specifics, but certainly by increasing our field reps by 20%, which I previously stated that our field was 50%. We increased it to 60%, at least amongst the key account manager. That allows us to go deeper and with more frequency to our higher decile position. So in terms of the 1,300, they are definitely on the target list, and there are some more above and beyond that on the target list as well.

彼得，我們不會給出具體細節，但肯定會將我們的現場代表數量增加 20%，而我之前說過我們的現場代表數量是 50%。我們將其提高到 60%，至少在大客戶經理中是如此。這使我們能夠更深入、更頻繁地達到更高的十分位。所以就這 1,300 人而言，他們肯定在目標名單上，而且還有一些超出目標名單的人。

Gil Blum, Needham & Company.

吉爾·布魯姆（Gil Blum），Needham & Company。

So maybe just one specific to treating physicians here. You mentioned the kind of feedback you've been receiving. Have there been any specific pushbacks of physicians who are less interested and have a follow-on?

所以也許這裡只有一個專門針對治療醫生的。您提到了您收到的回饋類型。有沒有醫生對此不太感興趣並有後續行動的具體反對意見？

Going back to the market research, what I would say is for those specifically that have not used RYTELO or not necessarily educated by our key account managers, some of the often cited barriers are cytopenias or not having patients.

回到市場調查，我想說的是，對於那些沒有使用過 RYTELO 或不一定接受過我們大客戶經理教育的人來說，一些經常提到的障礙是血球減少症或沒有患者。

However, that number dramatically changes when you talk about those physicians that have treated and or know about RYTELO. So we believe that continued reach frequency, delivery of strong messages, especially to our targeted accounts, will start to change those dynamics. But what I would key in on is the fact that physicians that have used it and are aware of RYTELO have a much more favorable view of the product profile and the utilization patterns.

然而，當你談到那些治療或了解 RYTELO 的醫生時，這個數字發生了巨大變化。因此，我們相信，持續的覆蓋頻率和強有力的訊息的傳遞（尤其是向我們的目標帳戶傳遞的訊息）將開始改變這些動態。但我要強調的是，使用過並了解 RYTELO 的醫生對該產品概況和使用模式的看法更加有利。

Just to hone in on that -- sorry, go ahead.

只是為了強調這一點——抱歉，請繼續。

If I may add, actually, we've had several engagements with physicians who have not used RYTELO. The main reason that they have accused it, as Jim said, is they're not aware of the full potential or they have heard about the cytopenia.

我可以補充一下，實際上，我們已經與幾位沒有使用過 RYTELO 的醫生進行了接觸。正如吉姆所說，他們指責它的主要原因是他們沒有意識到它的全部潛力，或者他們沒有聽說過血球減少症。

In those conversations we've had with many of those type of physicians, when we do discuss the mechanism of action and that the cytopenias are actually on target due to the mechanism of action, the whole attitude shifts and the potential for a disease modification drug for these patients does impact the physician thinking and potential utilization in their clinics.

在我們與許多此類醫生進行的對話中，當我們討論作用機制，並且由於作用機制，血球減少症實際上達到了目標時，整個態度發生了轉變，並且這些患者的疾病改良藥物的潛力確實影響了醫生的想法和他們在診所的潛在利用率。

So just to hone in on that message, would you say the main energy barrier here is just to get physicians to start treating? Is that fair?

那麼，為了進一步了解這一訊息，您是否認為這裡的主要能量障礙只是讓醫生開始治療？這樣公平嗎？

(multiple speakers)

（多位發言者）

One second, Jim. I mean, when [Revlizir] was launched, there was this so-called apathy among physicians converting from ESAs to spatter sets. To this day, we see patients, in particular in the community setting, on ESAs, even with high [EPO] levels, over 500, or patients who have failed ESAs. That's been the pattern for 20-plus years in the clinics, and that's the reason for many of those barriers that we are seeing initially in the spatter set journey, and some of that we're seeing for the imetelstat as well.

等一下，吉姆。我的意思是，當 [Revlizir] 推出時，從 ESA 轉向噴灑裝置的醫生們表現出了所謂的冷漠。直到今天，我們仍然可以看到，特別是在社區環境中，患者仍在使用 ESA，甚至 EPO 水平高達 500 以上，或 ESA 治療失敗。這是診所 20 多年來一直存在的模式，也是我們在濺鍍裝置發展歷程中最初看到的許多障礙的原因，也是我們在 imetelstat 中也看到的一些障礙的原因。

Go ahead, Jim.

繼續吧，吉姆。

Nothing to add. Thanks, Joe.

沒什麼好補充的。謝謝，喬。

Quick one for Michelle. I see OpEx guidance has not changed, even though you guys seem to be investing more in your sales force. Is this going to continue, or should we expect maybe a shifting more towards investment in G&A? Thank you.

米歇爾，快來吧。我發現營運支出指引沒有改變，儘管你們似乎在銷售隊伍上投入了更多資金。這種情況會持續下去嗎？或者我們應該預期投資會更多地轉向一般及行政管理（G&A）方面？謝謝。

Yeah, thanks. We had said previously that we had some levers to pull to maintain our OpEx guidance, particularly around some of our investment in inventory and manufacturing redundancy. We're going to be looking at all of that, but right now we have included all of the additional investment in commercial and medical, and we do not have to change our guidance.

是的，謝謝。我們之前曾說過，我們需要採取一些措施來維持我們的營運支出指導，特別是圍繞庫存和製造冗餘方面的一些投資。我們將考慮所有這些，但目前我們已經將所有額外投資納入了商業和醫療領域，我們不必改變我們的指導方針。

Stephen Willey, Stifel.

史蒂芬威利（Stephen Willey），Stifel。

I guess you talked about 900 accounts having order to date. Can you talk to, I guess, where those accounts fit within those prescribing buckets that you talked about? Are these accounts mostly in that top decile representing 50% of diagnosed patients? And then how does that 900 split out between academic and community?

我猜您說的是迄今為止已有 900 個帳戶。我想，您能否談談這些帳戶在您談到的處方範圍中處於什麼位置？這些帳戶是否大多位於代表確診患者 50% 的前十分位？那麼這 900 人如何在學術界和社群之間分配呢？

Yes, Stephen, thanks for the question. The majority of those accounts represented by the 900 are, in fact, on our target list. However, there are some that are not on our target list. In terms of the general split, it's reflective of the underlying dynamics, which is approximately one-third in the academic centers and two-thirds in the community.

是的，史蒂芬，謝謝你的提問。事實上，這 900 個帳戶中的大多數都在我們的目標名單上。然而，有些並不在我們的目標名單上。就整體劃分而言，它反映了潛在的動態，即學術中心約佔三分之一，社區約佔三分之二。

And what we expect going forward is that with increased personal and non-personal promotions and a focus on KOLs, that we actually grow both simultaneously. But our focus is both. We are focused on both the academic as well as the community.

我們期望未來隨著個人和非個人推廣的增加以及對關鍵意見領袖 (KOL) 的關注，我們實際上可以同時實現這兩項成長。但我們的重點是兩者。我們既關注學術，也關注社區。

Thanks for the question, Stephen.

謝謝你的提問，史蒂芬。

Okay. And then can you also just comment in terms of what you're seeing with respect to luspatercept utilization in the frontline setting, both in terms of RS positive and RS negative? And do you have any sense if these patients are subsequently stepping through an ESA as a second-line option, or is it just too early into the luspatercept frontline launch to have any real clarity here?

好的。然後，您能否就您所看到的有關 luspatercept 在前線環境中的利用情況（RS 陽性和 RS 陰性）發表評論？您是否知道這些患者隨後是否會將 ESA 作為二線治療選擇，或者現在推出 luspatercept 一線治療藥物還為時過早，無法真正弄清楚？

Thanks for the question. We do have that data. We've looked at it from a claims perspective. We haven't necessarily showed it. But I think what I could say is that we are seeing growth in the first line with luspatercept based upon the command data.

謝謝你的提問。我們確實有這些數據。我們從索賠的角度來看這個問題。我們不一定會表現出來。但我認為我可以說的是，根據命令數據，我們看到了 luspatercept 在第一線的成長。

And if that happens and continues to grow, we're expecting duration of treatment fairly consistent with their study. In terms of switch, we can't promote specifically post-luspatercept. Our labeled indication is ESA relapsed refractory or ESA ineligible. However, the NCCA guidelines is a bit broader.

如果這種情況發生並持續增長，我們預計治療持續時間將與他們的研究相當一致。在轉換方面，我們無法專門推廣 Luspatercept 後治療。我們的標籤適應症是 ESA 復發難治性或 ESA 不合格。然而，NCCA 的指導方針更為廣泛一些。

Emily Bodnar, H.C. Wainwright.

艾米麗·博德納、H.C. 溫賴特。

I'm curious for physicians who have used Ritolo and who are not reordering, which I believe you said was about one-third of them, are there any particular reasons that you've heard for why? And maybe if you can comment on discontinuation to date kind of reasonings for those and if that's kind of in line with your clinical data expectations.

我很好奇，對於那些使用過 Ritolo 並且沒有重新開藥的醫生來說，我相信您說過大約有三分之一的人，您是否聽說過有什麼特別的原因？也許您可以評論迄今為止停止這些研究的理由，以及這是否符合您的臨床數據預期。

Yeah, thanks, Emily. So in terms of dose interruptions, discontinuation based upon our patient chart audits and some of our market research, it appears largely that the commercial experience is reflective of the percentages seen in IMerge in our clinical trials. And what was the other part of the question?

是的，謝謝，艾米麗。因此，就劑量中斷、根據我們的患者圖表審計和一些市場研究而停止而言，商業經驗很大程度上反映了我們在臨床試驗中看到的 IMerge 的百分比。那麼問題的另一部分是什麼呢？

For the one-third of HCPs who you commented did not reorder RYTELO, if you can provide any reasonings that you're hearing for that.

對於您評論的三分之一的 HCP 沒有重新訂購 RYTELO，您是否可以提供您所聽到的任何理由。

Nothing specific at this point. It could just be simply a dose interruption due to a cytopenia. As you know, in this buy-and-bill market, we don't get perfect patient-level data. So what we do is market research, patient chart audits, and we triangulate those insights, and those insights seem to be consistent with IMerge. There aren't any new surprises in any of the data in market research.

目前還沒有什麼具體內容。這可能只是由於血球減少而導致的劑量中斷。如您所知，在這個購買和支付市場中，我們無法獲得完美的患者級數據。因此，我們所做的是市場研究、患者圖表審計，並對這些見解進行三角測量，這些見解似乎與 IMerge 一致。市場調查中的任何數據都沒有任何新的驚喜。

Okay. And then lastly, if you can comment on the improved MS data that you're going to have at ASCO, what differences should we be expecting for a presentation at ASH?

好的。最後，如果您可以評論一下在 ASCO 上即將獲得的改進型 MS 數據，那麼在 ASH 上進行演示時我們應該期待哪些不同？

I mean, we have started the second cohort, which is the established doses, which are the maximum tolerated doses of both drugs, which was a good surprise, if you will. And there were less cytopenia seen in that cohort of patients. So we are expanding, and we're adding additional JAK inhibitors to the combination.

我的意思是，我們已經開始了第二批研究，這是既定劑量，也是兩種藥物的最大耐受劑量，如果你願意的話，這是一個很好的驚喜。且該組患者中血球減少症的發生較少。因此我們正在擴大規模，並在組合中添加額外的 JAK 抑制劑。

Kalpit Patel, B. Riley Securities.

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

Maybe first on the inventory part of this, Michelle, I think you previously communicated that, you know, the distributors were maintaining two to four weeks of inventory in the channel. So what's the data supply today, I guess, or at the end of first quarter? And then I have a follow-up.

米歇爾，首先關於庫存部分，我想您之前已經說過，分銷商在渠道中維持著兩到四周的庫存。那我猜今天或第一季末的數據供應情況如何？然後我有一個後續問題。

Sure. Thanks, Kalpit. Yes. So at the end of Q4, as we mentioned, it was on the higher side. So it was on the higher end of the 3.5 weeks. And as of the end of Q1, it was on the lower end of 2 plus 2.5 weeks.

當然。謝謝，卡爾皮特。是的。因此，正如我們所提到的，在第四季末，它處於較高的水平。因此，它處於 3.5 週的較高水平。截至第一季末，這一時間處於 2 週加 2.5 週的較低水平。

Okay. Okay. Makes sense. At this point in the launch, are your new patient starts consistently exceeding the discontinuations? Or are you starting to see some of those early patients who received imetelstat start to roll off and offset the new starts?

好的。好的。有道理。在發布的這個階段，您的新患者開始數量是否一直超過停藥數量？或者您開始看到一些接受 imetelstat 治療的早期患者開始減少並抵消新開始治療的患者？

Kalpit, we don't have perfect data on this. Again, we use patient chart audits and marker research. In the buy-and-bill market, the data isn't at a patient-specific level.

Kalpit，我們對此沒有完美的數據。再次，我們使用患者圖表審計和標記研究。在購買和支付市場中，數據並不處於特定於患者的水平。

But I can tell you, and generally speaking, if 80% of the patients that I described in the previous quarter were third line plus, the duration of treatment for subsequent lines of therapy tend to be shorter than what we often quote as the median 7.8 months. So your math is correct. As they roll off, new patient starts have to fill the funnel and continue to drive.

但我可以告訴你，一般來說，如果我在上一季度描述的 80% 的患者是三線以上，那麼後續治療的治療時間往往會比我們通常引用的中位數 7.8 個月要短。所以你的數學是正確的。隨著他們的離開，新的病人必須填滿漏斗並繼續前進。

The promising data that I shared on this call is that based on most recent, new patient starts number 25%, approximately 25%, and we're in first and second line. So the earlier we move up in lines of therapy, we generally expect longer duration of treatment.

我在這次電話會議上分享的有希望的數據是，根據最近的數據，新患者的數量為 25%，大約是 25%，我們處於第一線和第二線。因此，我們越早開始治療，通常就能預期治療時間越長。

Okay. And then one financial question. You reported $19.8 million net loss for the quarter and had about $45 million in cash burn. Maybe walk us through what drove that incremental $25 million in outflow. Was this any capital changes or inventory build or something else?

好的。然後是一個財務問題。您報告本季淨虧損 1,980 萬美元，現金消耗約 4,500 萬美元。也許可以向我們介紹一下導致這 2500 萬美元流出的原因。這是任何資本變化或庫存增加還是其他什麼？

Well, Q1 cash burn is always higher due to payouts of bonuses and some early investment, yes, on the inventory side. That was front (inaudible)

嗯，由於獎金的支付和庫存方面的一些早期投資，第一季的現金消耗總是較高。那是前面（聽不清楚）

Faisal Khurshid, Leerink Partners.

Faisal Khurshid，Leerink Partners。

Hey, guys, thanks for taking the question. I just wanted to ask about this 10% demand increase that you've seen in April. Could you comment on sort of how sustainable you see that increase to be going forward and also, like, how reliably do you expect it to translate into, like, true revenue growth?

嘿，夥計們，謝謝你們回答這個問題。我只是想問一下您在四月看到的 10% 的需求成長。您能否評論一下您認為這種成長在未來的可持續性如何，以及您預計它轉化為真正的收入成長的可靠性如何？

Thanks, Faisal. It's a great question. It's one data point. It's a promising data point, April over March. What I can tell you is that from a sales force perspective in market research, delivering the right message to the right positions is leading to success. We saw the changes in perceptions that I described earlier. We're seeing at least this one data point of April over March growth.

謝謝，費薩爾。這是一個很好的問題。這是一個數據點。四月份的數據與三月相比有明顯改善，這是一個很有希望的數據點。我可以告訴你的是，從市場研究的銷售人員角度來看，向正確的職位傳遞正確的訊息是成功的關鍵。我們看到了之前我所描述的觀念上的變化。我們至少看到四月的一個數據點比三月有所成長。

The key for all of us is to sustain that growth and build the momentum going forward. Our expectation is that as a team that we return to growth based upon strong execution.

對我們所有人來說，關鍵是保持這種成長勢頭並不斷向前發展。我們的期望是，作為一個團隊，我們能夠基於強大的執行力來恢復成長。

That is all the time we have for questions. This concludes today's conference call. Thank you for joining. You may now disconnect.

我們回答問題的時間就這麼多了。今天的電話會議到此結束。感謝您的加入。您現在可以斷開連線。