Geron Corp (GERN) 2024 Q2 法說會逐字稿

Hello and welcome to the Geron Corporation second-quarter 2024 earnings call. (Operator Instructions) I would now like to turn the conference over to Aron Feingold, vice president of investor relations and corporate communication. You may begin.

您好，歡迎參加 Geron Corporation 2024 年第二季財報電話會議。（操作員指示）我現在想將會議交給投資者關係和企業傳播副總裁 Aron Feingold。你可以開始了。

Good morning, everyone. Welcome to the Geron Corporation second-quarter 2024 earnings conference call. I am Aron Feingold, Geron's vice president of investor relations and corporate communication. I'm joined today by several members of Geron's management team.

大家早安。歡迎參加 Geron Corporation 2024 年第二季財報電話會議。我是 Aron Feingold，Geron 負責投資者關係和企業傳播的副總裁。今天，Geron 管理團隊的幾位成員也加入了我的行列。

Dr. John Scarlett, chairman and chief executive officer; Dr. Andrew Grethlein, executive vice president and chief operating officer; Dr. Faye Feller, executive vice president and chief medical officer; and Michelle Robertson, executive vice president and chief financial officer.

約翰‧史嘉莉博士，董事長兼執行長； Andrew Grethlein 博士，執行副總裁兼營運長； Faye Feller 博士，執行副總裁兼首席醫療官；以及執行副總裁兼財務長米歇爾·羅伯遜。

On today's call, Chip will start off with introductory remarks on commercial execution and value creation. Andy will provide a commercial and operations update. Faye will speak to medical and clinical updates, Michelle will provide a financial review, and Chip will close with some final remarks.

在今天的電話會議上，奇普將首先就商業執行和價值創造進行介紹性發言。安迪將提供商業和營運方面的最新資訊。Faye 將介紹醫療和臨床最新情況，Michelle 將提供財務審查，Chip 將發表一些最後的評論。

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 relating 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 fact.

在開始之前，請注意，在本次演示和問答環節中，我們將就未來的活動、業績、計劃、期望和其他預測做出前瞻性陳述，包括與發布相關的陳述， Rytelo 的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 的財務資源是否充足以及其他不屬於歷史事實的陳述。

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 filed with the SEC, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. 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，我建議您參考 Geron 向美國證券交易委員會提交的最新定期報告中「風險因素」標題下的討論，該報告指出了可能導致實際結果與前瞻性陳述中包含的結果存在重大差異的重要因素。Geron 不承擔更新我們的前瞻性聲明的責任或義務。

With that, I'll turn the call over to Chip. Chip?

這樣，我會將電話轉給 Chip。晶片?

Thanks, Aron. Good morning, everyone. Thanks for joining us. It was just eight weeks ago that FDA approved Rytelo, our branded name for imetelstat, as the first and only telomerase, and it was just six weeks ago that Rytelo became commercially available in the US.

謝謝，阿倫。大家早安。感謝您加入我們。就在八週前，FDA 批准了 Rytelo（我們的 imetelstat 品牌名稱）作為第一個也是唯一的端粒酶，而就在六週前，Rytelo 在美國上市。

With our strong commercial infrastructure in place at launch and the efficient mobilization of our field teams, we've seen encouraging early launch results. As of July 31, 60% of the top decile 1 to 4 accounts had been reached by our team across both community and academic settings.

憑藉我們強大的商業基礎設施在啟動時到位以及我們現場團隊的高效動員，我們已經看到了令人鼓舞的早期啟動結果。截至 7 月 31 日，我們的團隊已經在社區和學術環境中接觸到了 60% 的前十分之一到 4 的帳戶。

This has led to gratifying uptake. We estimate, again, as of July 31, that approximately 160 patients have received Rytelo, which is quite encouraging given the very early stage of this launch.

這帶來了可喜的採用率。我們再次估計，截至 7 月 31 日，約有 160 名患者已接受 Rytelo 治療，鑑於該產品尚處於早期階段，這相當令人鼓舞。

The enthusiastic reception for Rytelo that we've seen within the hematology community reinforces the unmet needs for lower-risk MDS patients with symptomatic transfusion-dependent anemia. Many of our customers are passionate about getting access to Rytelo for their patients, and we've seen a strong push across the US to add Rytelo to formularies, treatment pathways, and EMRs, including in the community setting.

我們在血液學界看到的對 Rytelo 的熱烈歡迎進一步強化了患有症狀性輸血依賴性貧血的低風險 MDS 患者未得到滿足的需求。我們的許多客戶都熱衷於讓他們的患者使用 Rytelo，我們看到美國各地大力推動將 Rytelo 添加到處方集、治療途徑和 EMR 中，包括在社區環境中。

In addition, the MDS NCCN Guidelines were updated this July 25 to include Rytelo as a Category 1 and 2A treatment for lower-risk MDS patients.

此外，MDS NCCN 指南於今年 7 月 25 日進行了更新，將 Rytelo 納入低風險 MDS 患者的 1 類和 2A 類治療藥物。

That is, Rytelo is now designated for use in both RS positive and RS negative first-line ESA ineligible patients, as well as in both RS positive and RS negative second-line patients, regardless of prior first-line treatment.

也就是說，Rytelo 現在被指定用於 RS 陽性和 RS 陰性一線 ESA 不合格患者，以及 RS 陽性和 RS 陰性二線患者，無論之前是否接受過一線治療。

We believe that these favorable NCCN Guidelines have put Rytelo in a strong competitive position. During their portions of this call today, Andy and Faye will walk through how clinical, formulary and treatment pathway decision-making is guided by the NCCN Guidelines.

我們相信，這些有利的 NCCN 指南使 Rytelo 處於強大的競爭地位。在今天的電話會議中，Andy 和 Faye 將介紹如何根據 NCCN 指南指導臨床、處方和治療路徑決策。

With the introduction of Rytelo as a new therapeutic option, we're seeing increasing dialogue among hematologists, rethinking treatment approaches for eligible low-risk MDS patients with transfusion-dependent anemia.

隨著 Rytelo 作為一種新的治療選擇的推出，我們看到血液學家之間的對話越來越多，重新思考患有輸血依賴性貧血的低風險 MDS 患者的治療方法。

Consequently, we believe that Rytelo can become part of the standard of care for both eligible first and second-line patients. As shown on this slide, from the approximately 13,200 US patients with lower-risk MDS who need treatment for symptomatic anemia, approximately one in 10 are ESA ineligible due to serum EPO levels higher than 500 mU/mL. These first-line patients have limited treatment options.

因此，我們相信 Rytelo 可以成為符合條件的第一線和二線患者護理標準的一部分。如這張投影片所示，在大約 13,200 名需要治療症狀性貧血的低風險 MDS 患者中，大約十分之一的人因血清 EPO 水平高於 500 mU/mL 而不符合 ESA 資格。這些一線患者的治療選擇有限。

RS-positive patients make up approximately 25% of the lower-risk MDS patient population, many of whom continue to experience high transfusion burden despite available therapies. RS-negative patients make up approximately 75% of lower-risk MDS patient populations, many of whom are particularly vulnerable to poor clinical outcomes and have few other treatment options. In support of our commercial opportunity, we believe we have strong regulatory extensivity and patent protection in the US for Rytelo for this disease.

RS 陽性患者約佔低風險 MDS 患者群體的 25%，儘管有可用的治療方法，但其中許多人仍然承受著較高的輸血負擔。RS陰性患者約佔低風險MDS患者族群的75%，其中許多人特別容易出現不良的臨床結果，幾乎沒有其他治療選擇。為了支持我們的商業機會，我們相信我們在美國針對 Rytelo 這種疾病擁有強大的監管廣泛性和專利保護。

Following approval, we completed the listing of our patents in the FDA's Orange Book. We also received confirmation from the FDA of imetelstat's orphan drug exclusivity for lower-risk MDS into June of 2031. We've also filed our applications for patent term extension or PTE, including for our method of use patent covering MDS and MS. If the PTE application is granted and applied to this patent, we estimate that the patent term would extend through August of 2037.

獲得批准後，我們完成了將我們的專利列入 FDA 橙皮書的工作。我們也收到 FDA 的確認，即 imetelstat 的低風險 MDS 孤兒藥獨佔權有效期至 2031 年 6 月。我們也提交了專利期限延長或 PTE 申請，包括涵蓋 MDS 和 MS 的使用方法專利。如果PTE申請獲得批准並應用於該專利，我們預計專利期限將延長至2037年8月。

We believe this IT protection, as well as several key factors I'll discuss on the next slide, position us well to create long-term commercial value with Rytelo. Based on the clinical profile of Rytelo, the approved US prescribing information, and now a great set of NCCN Guidelines, we believe we are well-positioned to build long-term commercial value with Rytelo.

我們相信這種 IT 保護以及我將在下一張幻燈片中討論的幾個關鍵因素使我們能夠很好地與 Rytelo 一起創造長期商業價值。基於 Rytelo 的臨床概況、已批准的美國處方資訊以及現在的一套優秀的 NCCN 指南，我們相信我們已經做好了與 Rytelo 建立長期商業價值的準備。

More specifically, first, there's a high unmet treatment need for patients with lower-risk MDS as many patients progress and do not respond to current treatments, achieve a durable response, or experience extended and continuous red blood cell transfusion independence.

更具體地說，首先，低風險骨髓增生異常綜合症患者的治療需求未被滿足，因為許多患者病情進展，對目前的治療沒有反應，無法實現持久的反應，或經歷長期和持續的紅血球輸注獨立性。

Treatment options for red blood cell transfusion independence patients who are relapsed or refractory to or ineligible for ESA can have significant limitations underscoring the need for novel treatment options such as Rytelo.

對於復發或難治性或不適合 ESA 的紅血球輸注獨立患者的治療選擇可能具有顯著的局限性，這凸顯了對 Rytelo 等新型治療選擇的需求。

Second, as demonstrated by the totality of clinical benefits in the IMerge Phase 3 clinical trial, Rytelo can offer eligible low-risk MDS patients meaningful clinical benefits, including durable and sustained red blood cell transfusion independence and reduction in transfusion burden.

其次，正如 IMerge 3 期臨床試驗的整體臨床益處所證明的那樣，Rytelo 可以為符合條件的低風險 MDS 患者提供有意義的臨床益處，包括持久且持續的紅血球輸注獨立性和減少輸血負擔。

In IMerge, this treatment effect is consistent across key lower-risk MDS subgroups, including both RS-positive and RS-negative patients who are not eligible for ESAs, as well as both RS-positive and RS-negative patients who are relapsed or refractory to ESAs. Rytelo was also shown in IMerge phase 3 to have a well-characterized safety profile with generally manageable and short-lived Thrombocytopenia, Neutropenia, which are familiar adverse events for hematologists who are experienced with managing cytopenias.

在 IMerge 中，這種治療效果在關鍵的低風險 MDS 亞組中是一致的，包括不符合 ESA 資格的 RS 陽性和 RS 陰性患者，以及復發或難治性的 RS 陽性和 RS 陰性患者到歐洲航天局。IMerge 3 期試驗還表明，Rytelo 具有良好的安全性，一般可控制且短暫的血小板減少症、中性粒細胞減少症，這對於在處理血球減少症方面經驗豐富的血液學家來說是常見的不良事件。

Third, from an EU perspective, we also have a marketing authorization application, or MAA, under review and transfusion independent lower-risk MDS, which we expect could be completed in early 2025. We're working to finalize our strategy for EU commercialization as we continue to explore our options in the interest of maximizing our ability to serve all of our stakeholders, patients, healthcare providers, and shareholders.

第三，從歐盟的角度來看，我們還有正在審查的行銷授權申請（MAA）和獨立於輸血的低風險 MDS，我們預計可以在 2025 年初完成。我們正在努力敲定我們的歐盟商業化策略，同時繼續探索我們的選擇，以最大限度地提高我們為所有利益相關者、患者、醫療保健提供者和股東提供服務的能力。

We're continuing to engage in discussions with EU regulators, authorities, and payers as we assess those options, which include self-commercialization or partnering. Then fourth, from a clinical development perspective, our pivotal Phase 3 IMpactMF OS clinical trial in JAK inhibitor relapsed/refractory myelofibrosis patients has now achieved approximately 70% enrollment.

在評估這些選項（包括自我商業化或合作）時，我們將繼續與歐盟監管機構、當局和付款人進行討論。第四，從臨床開發的角度來看，我們針對 JAK 抑制劑復發/難治性骨髓纖維化患者的關鍵 3 期 IMpactMF OS 臨床試驗現已實現約 70% 的入組率。

And interim analysis is still expected in early '26. This JAK I relapsed or refractory MF population represents a high-end met need population and significant commercial opportunity. Lastly, our highly experienced team is driving performance across our business, passionately serving patients and customers, and staying focused on quality and operational excellence.

中期分析預計仍將在 26 年初進行。此 JAK I 復發或難治性 MF 族群代表了高端滿足需求族群和重要的商業機會。最後，我們經驗豐富的團隊正在推動整個業務的績效，熱情地為患者和客戶服務，並始終專注於品質和卓越營運。

I'm also happy to report today that we have had an exceptionally strong response to our Chief Commercial Officer search, and that we've made great progress in identifying several candidates with strong leadership skills and a history of outstanding commercial execution.

我今天也很高興地向大家報告，我們對首席商務官的搜尋得到了異常強烈的回應，並且我們在確定幾位具有強大領導能力和傑出商業執行歷史的候選人方面取得了巨大進展。

We expect to be able to make an announcement in the next month or so. With that, I'll turn the call over to Andy for commercial and operations update. Andy?

我們預計能夠在下個月左右發佈公告。這樣，我會將電話轉給安迪，以獲取商業和營運方面的最新資訊。安迪？

Thanks, Chip. Good morning to everyone on the call. We have built a strong commercial infrastructure that has enabled us to activate the launch effectively. First, we are pleased with the early awareness of Rytelo among prescribers and payers.

謝謝，奇普。各位來電的人早安。我們建立了強大的商業基礎設施，使我們能夠有效地啟動發布。首先，我們對 Rytelo 在處方者和付款人中的早期認識感到高興。

Based on our market research before FDA approval in May of 2024 of over 100 US hematologists and oncologists, over 80% of those surveyed were aware of the imetelstat. One in three surveyed physicians indicated familiarity with the clinical data, and a majority of these physicians looked favorably on the efficacy profile and mechanism of action, which is especially important for first-in-class treatment. Payers are expressing high levels of interest and already have a strong understanding of the Rytelo US prescribing information and IMerge Phase 3 clinical data.

根據我們在 2024 年 5 月 FDA 批准之前對 100 多名美國血液學家和腫瘤學家進行的市場調查，超過 80% 的受訪者了解 imetelstat。三分之一的受訪的醫生表示熟悉臨床數據，其中大多數醫生看好療效概況和作用機制，這對於一流的治療尤其重要。付款人表現出很高的興趣，並且已經對 Rytelo US 處方資訊和 IMerge 3 期臨床數據有了深入的了解。

From an operational perspective, both dosage strengths of Rytelo, the 188 mg vial and 47 mg vials were available in our distribution channel for customers to order from specialty distributors as of June 27, 2024. Our distribution network is fully activated with our specialty distributor network actively supporting customer demand across hospitals and community oncology clinics.

從營運角度來看，截至 2024 年 6 月 27 日，Rytelo 的兩種劑量規格（188 毫克小瓶和 47 毫克小瓶）均可在我們的分銷管道中供客戶向專業分銷商訂購。我們的分銷網絡已完全激活，我們的專業分銷商網絡積極支持醫院和社區腫瘤診所的客戶需求。

Across the contiguous 48 states, Rytelo is available to HCPs within 24 to 48 hours from our specialty distribution networks.

在鄰近的 48 個州，HCP 可在 24 至 48 小時內透過我們的專業分銷網絡獲得 Rytelo。

We also believe that Rytelo's inclusion in the updated NCCN Guidelines has been important in spreading awareness among the prescriber community. The NCCN Guidelines are a highly regarded resource in clinical decision-making for prescribers as well as provide critical considerations from a formulary and treatment pathway development perspective.

我們也認為，將 Rytelo 納入更新後的 NCCN 指引對於在處方者群體中傳播認識非常重要。NCCN 指南是處方醫生臨床決策中備受推崇的資源，並從處方和治療途徑開發的角度提供了關鍵考慮因素。

Generally, the top national payers and Medicare cover oncology medicines categorized as 1 or 2A treatment by NCCN Guidelines. Our patient access and affordability solutions are fully activated.

一般來說，最高的國家支付者和醫療保險承保被 NCCN 指南歸類為 1 或 2A 治療的腫瘤藥物。我們的患者訪問和負擔能力解決方案已全面啟動。

Our patient hub is fully operational and supporting inquiries from HCPs and patients. Our J-code application was submitted in July 2024 and we expect issuance of a permanent J-code in the first quarter of 2025. We have seen a strong push by prescribers to add Rytelo to their formularies and EMRs that can help accelerate access in the meantime.

我們的患者中心已全面投入運營，並支持醫護人員和患者的詢問。我們的 J 代碼申請已於 2024 年 7 月提交，我們預計將在 2025 年第一季發布永久 J 代碼。我們看到處方醫生大力推動將 Rytelo 添加到他們的處方集和電子病歷中，這有助於同時加快獲取速度。

Lastly, we engage with the major national payers within 30 days of launch and look forward to continued dialogue as they adopt their national coverage policies, which we expect to occur in the first quarter of 2025.

最後，我們在啟動後 30 天內與主要的國家付款人進行接觸，並期待在他們採用國家覆蓋政策時繼續對話，我們預計這將在 2025 年第一季發生。

On this next slide is a snapshot of our medical and commercial field teams that have been fully deployed to cover the entire US market, supporting HCP and account education and uptake. This includes 50 Key Account Managers, our Oncology Clinical Educator Liaisons, Field Reimbursement Access Directors & National Accounts, along with our Field Medical Affairs Teams.

下一張投影片是我們的醫療和商業現場團隊的快照，這些團隊已全面部署以涵蓋整個美國市場，支援 HCP 和客戶教育和吸收。這包括 50 名大客戶經理、我們的腫瘤學臨床教育聯絡員、現場報銷總監和國民帳戶，以及我們的現場醫療事務團隊。

We are pleased that since these commercial and medical field teams were deployed in June, there has been a strong level of in-person access to community and academic accounts and HCPs.

我們很高興地看到，自從這些商業和醫療現場團隊在 6 月部署以來，人們能夠親自接觸社區和學術帳戶以及 HCP。

We believe that the experience and relationships that our talented field teams bring to Geron have enabled them to quickly access these accounts. We believe that the strong Rytelo value proposition, commercial foundation, and the execution of our entire organization is driving encouraging early results over these first six weeks of launch.

我們相信，我們才華橫溢的現場團隊為 Geron 帶來的經驗和關係使他們能夠快速存取這些帳戶。我們相信，強大的 Rytelo 價值主張、商業基礎和我們整個組織的執行力正在推動發布前六週的令人鼓舞的早期成果。

As we commented earlier, we estimate that as of July 31, 2024, approximately 160 patients have received Rytelo. This demand was generated in part by reaching approximately 60% of top decile 1 to 4 accounts and includes orders from roughly 115 unique accounts.

正如我們之前評論的那樣，我們估計截至 2024 年 7 月 31 日，約有 160 名患者接受了 Rytelo 治療。這項需求部分是透過達到前十分之一至 4 名帳戶中約 60% 的需求而產生的，其中包括來自約 115 個唯一帳戶的訂單。

We are seeing an encouraging range of customers ordering Rytelo in these early days, from small community to large aggregator accounts, with hospitals ranging from community, academic centers, teaching hospitals, and large health systems.

我們看到早期訂購 Rytelo 的客戶範圍令人鼓舞，從小型社區到大型聚合商帳戶，醫院包括社區、學術中心、教學醫院和大型健康系統。

In July, we kicked off our National Speakers Program with the launch of our National Broadcast Event featuring medical experts, which garnered over 300 medical professional participants. These events are a critical component of our marketing strategy to make sure HCPs are aware of the new treatment option for their eligible patients.

7 月，我們啟動了由醫學專家參加的全國廣播活動，拉開了全國演講者計畫的序幕，吸引了 300 多名醫學專業人士參加。這些活動是我們行銷策略的重要組成部分，以確保 HCP 了解適合其符合條件的患者的新治療選擇。

Overall, our teams have focused on delivering our launch strategic objectives, supporting a positive first experience for HCPs and patients, encouraging adoption among prescribers, and facilitating patient access. We believe our early performance reinforces that executing against these objectives can meaningfully drive awareness and uptake for appropriate patients.

總體而言，我們的團隊專注於實現我們的啟動策略目標，支持醫護人員和患者獲得積極的初次體驗，鼓勵處方者採用，並促進患者就診。我們相信，我們的早期表現強化了執行這些目標可以有意義地提高適當患者的認識和吸收。

With that, I'll turn the call over to Faye for a medical and clinical update. Faye?

這樣，我會將電話轉給 Faye，以了解醫療和臨床最新情況。菲？

Thanks, Andy. And thanks to everyone for joining our call today. As Chip mentioned, on July 25, the NCCN published updated MDS treatment guidelines, including Rytelo for the treatment of symptomatic anemia in patients with lower-risk MDS.

謝謝，安迪。感謝大家今天加入我們的電話會議。正如 Chip 所提到的，7 月 25 日，NCCN 發布了更新的 MDS 治療指南，其中包括 Rytelo 用於治療低風險 MDS 患者的症狀性貧血。

We believe that Rytelo's placement in the updated NCCN Guidelines reflects the strength of our Phase 3 data, which showed the clinical benefit of imetelstat regardless of ring sideroblast status or serum EPO level, as well as the favorable US prescribing information, where Rytelo is indicated broadly across RS positive and RS negative patients who are both ESA ineligible and ESA relapsed or refractory.

我們相信，Rytelo 在更新後的NCCN 指南中的排名反映了我們3 期數據的實力，這些數據顯示了imetelstat 的臨床益處，無論環形鐵粒幼細胞狀態或血清EPO 水平如何，以及有利的美國處方信息，其中Rytelo 被廣泛適應涵蓋既不符合 ESA 資格又患有 ESA 復發或難治性的 RS 陽性和 RS 陰性患者。

The MDS NCCN Guidelines characterize lower-risk MDS patients without the del(5q) abnormality and with symptomatic anemia on the basis of ring sideroblast status and serum EPO levels without specifying red blood cell transfusion burden.

MDS NCCN 指引根據環形鐵粒幼細胞狀態和血清 EPO 水平來描述無 del(5q) 異常且有症狀性貧血的低風險 MDS 患者，但未指定紅血球輸注負擔。

Overall, and as shown in the purple comment boxes on the far right of this slide, these updated MDS NCCN treatment guidelines include Rytelo as a Category 2A treatment for both RS positive and RS negative first-line ESA ineligible patients and as a Category 1 treatment for both RS positive and RS negative second-line patients, regardless of first-line therapy. Diving into these guidelines in more detail.

總體而言，如本幻燈片最右側的紫色評論框所示，這些更新的 MDS NCCN 治療指南包括 Rytelo 作為 RS 陽性和 RS 陰性一線 ESA 不合格患者的 2A 類治療，以及作為 1 類治療對於RS陽性和RS 陰性二線患者，無論一線治療如何。更詳細地深入研究這些指南。

On the left side of the slide is a schematic representing the NCCN Guidelines for the treatment of RS positive patients. For ESA-ineligible patients who have serum EPO levels greater than 500 mU/mL, imetelstat is included as a Category 2A first-line treatment.

幻燈片左側是代表 RS 陽性患者治療的 NCCN 指引的示意圖。對於不符合 ESA 條件且血清 EPO 水準高於 500 mU/mL 的患者，imetelstat 被列為 2A 類第一線治療。

For RS-positive ESA eligible patients with serum EPO levels 500 mU/mL and below, imetelstat is included as a Category 1 treatment second-line after luspatercept. Additionally, as shown in the 2-plus line at the bottom of the schematic, imetelstat is included as a Category 1 treatment for later lines of therapy after ESA or luspatercept treatment in these RS-positive ESA-eligible patients.

對於血清 EPO 水平為 500 mU/mL 及以下的 RS 陽性 ESA 患者，imetelstat 被列為繼 luspatercept 之後的 1 類二線治療。此外，如示意圖底部的 2+ 線所示，對於這些符合 ESA 資格的 RS 陽性患者，在 ESA 或 luspatercept 治療後，將 imetelstat 作為 1 類治療藥物納入後續治療方案。

On the right side of the slide is a schematic representing the NCCN Guidelines for RS-negative patients. For ESA-ineligible patients who have serum EPO levels greater than 500 mU/mL, imetelstat is included as a Category 2A first-line treatment.

幻燈片右側是代表 RS 陰性患者的 NCCN 指引的示意圖。對於不符合 ESA 條件且血清 EPO 水準高於 500 mU/mL 的患者，imetelstat 被列為 2A 類第一線治療。

For RS negative ESA eligible patients with serum EPO levels 500 mU/mL and below, imetelstat is included as a Category 1 treatment regardless of prior first-line therapy with either ESAs or luspatercept. Turning now to a clinical development update from our myelofibrosis program.

對於符合 RS 陰性 ESA 且血清 EPO 水平為 500 mU/mL 及以下的患者，無論之前是否接受過 ESA 或 luspatercept 一線治療，imetelstat 均被列為 1 類治療。現在轉向我們的骨髓纖維化項目的臨床開發更新。

Our pivotal Phase 3 IMpactMF trial of imetelstat in JAK inhibitor relapsed/refractory MS, the first and only Phase 3 trial in MS with overall survival as a primary endpoint, has reached approximately 70% enrollment as of August 2024.

我們的imetelstat 治療JAK 抑制劑復發/難治性多發性硬化症的關鍵3 期IMpactMF 試驗是第一個也是唯一一個以總存活期為主要終點的多發性硬化症3 期試驗，截至2024 年8 月，入組率已達約70%。

A per-protocol interim analysis has been planned when approximately 35% of the planned enrolled patients have died, which we anticipate in early 2026. A final analysis is planned when approximately 50% of the planned enrolled patients have died, which is currently anticipated in early 2027. If the interim analysis is statistically significant, we would plan to file a supplemental new drug application with the FDA based on the interim analysis.

當大約 35% 的計劃入組患者死亡時（我們預計在 2026 年初），我們計劃進行符合方案的中期分析。計劃在大約 50% 的計劃入組患者死亡後進行最終分析，目前預計在 2027 年初。如果中期分析具有統計意義，我們將計劃根據中期分析向 FDA 提交補充新藥申請。

As an overall survival study, the timeline for the interim and final analyses is dependent not only on the rate of enrollment, but also on the event rate or patient death rate in the trial. Today, treatment in myelofibrosis is dominated by JAK inhibitors or therapies with other mechanisms of action in combination with JAK inhibitors.

作為一項整體存活研究，中期和最終分析的時間表不僅取決於入組率，還取決於試驗中的事件發生率或患者死亡率。如今，骨髓纖維化的治療以 JAK 抑制劑或其他作用機制與 JAK 抑制劑合併治療為主。

Once patients become unresponsive to JAK inhibitors, which leads to treatment discontinuation for approximately 75% of patients after five years, they face a dismal overall survival of approximately 11 to 16 months. We believe that if our trial is successful and imetelstat is approved in this indication, it could transform treatment for these myelofibrosis patients.

一旦患者對 JAK 抑制劑無反應，導致約 75% 的患者在五年後停止治療，他們將面臨約 11 至 16 個月的慘淡總生存期。我們相信，如果我們的試驗成功並且 imetelstat 在該適應症中獲得批准，它可能會改變這些骨髓纖維化患者的治療方法。

Lastly, we are also evaluating imetelstat in the ImproveMF Phase 1 study, a combination therapy with ruxolitinib in patients with frontline myelofibrosis. Our main goal for this combination study is to determine the safety profile of the regimen of ruxolitinib and imetelstat, as well as to explore potential activity of imetelstat in a frontline MS disease setting.

最後，我們也在 ImproveMF 1 期研究中評估 imetelstat，這是一種與魯索替尼合併治療第一線骨髓纖維化患者的藥物。我們這項聯合研究的主要目標是確定魯索替尼和 imetelstat 方案的安全性，並探索 imetelstat 在第一線 MS 疾病環境中的潛在活性。

Part 1 of the study is designed to be dose-finding. In July 2024, after no dose-limiting toxicities were experienced by the first three patients in the dose level 4 cohort, or imetelstat sodium 9.4 mg/kg, the Study Evaluation Team, or SET, unanimously recommended expanding the cohort per the trial protocol.

研究的第 1 部分旨在尋找劑量。2024 年 7 月，劑量水平 4 隊列或伊美司他鈉 9.4 mg/kg 的前三名患者未出現劑量限制性毒性後，研究評估小組 (SET) 一致建議按照試驗方案擴大隊列。

This is the final step before dose selection and progression to Part 2 of the study that is designed for expansion and dose confirmation. We hope to provide an update from Part 1 of the study at an upcoming medical meeting.

這是劑量選擇和進入研究第二部分之前的最後一步，該部分旨在擴展和劑量確認。我們希望在即將召開的醫學會議上提供該研究第 1 部分的最新資訊。

With that, I'll turn the call over to Michelle for a financial update. Michelle?

這樣，我會將電話轉給米歇爾，以了解最新的財務狀況。米歇爾？

Thanks, Faye. Good morning, everyone. For detailed Q2, 2024 financials please refer to the press release we issued this morning, which is available on our website. Now let me bring your attention to a few highlights from the quarter.

謝謝，費耶。大家早安。有關 2024 年第二季的詳細財務數據，請參閱我們今天早上發布的新聞稿，該新聞稿可在我們的網站上找到。現在讓我提請您注意本季的一些亮點。

As of June 30, 2024, the company had approximately $430 million in cash, cash equivalents, and marketable securities, total product revenue net for the three and six months ended June 30, 2024, was approximately $780,000. Rytelo became available for prescribers to order from specialty distributors as of June 27th, 2024.

截至2024年6月30日，該公司擁有約4.3億美元的現金、現金等價物和有價證券，截至2024年6月30日的三個月和六個月的產品淨收入總額約為78萬美元。自 2024 年 6 月 27 日起，處方醫生可以向專業經銷商訂購 Rytelo。

Total revenues for the three and six months ending June 30th were $882,000 and $1.2 million, compared to $29,000 and $50,000 for the same period in 2023. The increase in revenue is due to product revenue from US sales of Rytelo that commenced in June 2024.

截至 6 月 30 日的三個月和六個月的總收入分別為 882,000 美元和 120 萬美元，而 2023 年同期為 29,000 美元和 50,000 美元。收入增加是由於 Rytelo 自 2024 年 6 月開始在美國銷售的產品收入。

Total operating expenses for the three and six months ended June 30 were $70.2 million and $126.7 million, compared to $52 million and $92.1 million for the same period in 2023. Cost of goods sold was approximately $17,000 for the three and six months ended June 30, which consisted of cost to manufacture and distribute Rytelo. R&D expenses for the three months and six months ended June 30, 2024, were $30.8 million and $60.2 million, respectively, and $35.5 million and $62.7 million for the same period in 2023.

截至 6 月 30 日的三個月和六個月的總營運費用分別為 7,020 萬美元和 1.267 億美元，而 2023 年同期為 5,200 萬美元和 9,210 萬美元。截至 6 月 30 日的三個月和六個月，銷售成本約為 17,000 美元，其中包括製造和分銷 Rytelo 的成本。截至2024年6月30日的三個月和六個月的研發費用分別為3,080萬美元和6,020萬美元，2023年同期為3,550萬美元和6,270萬美元。

Our clinical development costs for IMerge Phase 3 have decreased as we move into the long-term follow-up stage. Selling, general, and administrative expenses for the three and six months ended June 30, 2024, with $39.4 million and $66.5 million, respectively, and $16.5 million and $29.4 million for the same period in 2023.

隨著我們進入長期追蹤階段，我們的 IMerge 第 3 期臨床開發成本已經下降。截至2024年6月30日的三個月和六個月的銷售、一般和管理費用分別為3,940萬美元和6,650萬美元，2023年同期為1,650萬美元和2,940萬美元。

The increase in selling, general, and administrative expenses primarily reflects higher commercial launch expenses, increases in headcount, and stock-based compensation, recognized due to the vesting of performance-based stock options upon FDA approval of Rytelo. As of June 30, 2024, we had 220 full-time employees.

銷售、一般和管理費用的增加主要反映了商業啟動費用的增加、員工人數的增加以及基於股票的薪酬，這些費用是由於 FDA 批准 Rytelo 後基於績效的股票期權的歸屬而確認的。截至2024年6月30日，我們擁有220名全職員工。

We plan to grow to a total of approximately 230 to 260 employees by year-end 2024. Our projected full-year 2024 operating expenses are expected to be between $270 million and $280 million, which is unchanged from our prior guidance.

我們計劃在 2024 年底員工總數增加到約 230 至 260 名。我們預計 2024 年全年營運費用預計在 2.7 億美元至 2.8 億美元之間，與我們先前的指引一致。

Based on our current operating plans and assumptions, we believe that our existing cash, cash equivalents, and marketable securities, together with our projected revenues from US sales of Rytelo, will be sufficient to fund our projected operating requirements into the second quarter of 2026.

根據我們目前的營運計劃和假設，我們相信我們現有的現金、現金等價物和有價證券，加上我們在美國銷售 Rytelo 的預期收入，將足以滿足我們到 2026 年第二季的預期營運需求。

I will now turn the call back over to Chip.

我現在將把電話轉回給奇普。

Thanks, Michelle. To close, we're encouraged by our early commercial launch performance and the feedback we're receiving from customers and payers. We're pleased with our strong execution to date, but also recognize that we're still in the very early stages of our US launch, with many more patients to serve and many more customers to engage.

謝謝，米歇爾。最後，我們對早期商業發布的表現以及從客戶和付款人收到的回饋感到鼓舞。我們對迄今為止的強勁執行力感到滿意，但也意識到我們仍處於美國推出的早期階段，需要服務更多患者，需要吸引更多客戶。

We have conviction that Rytelo can become part of the standard of care for eligible patients in this high-end need, lower-risk MDS treatment paradigm and bring differentiated benefits to patients. And in addition to our launch in lower-risk MDS, we're also advancing our imetelstat development program in myelofibrosis, which, having positive outcomes from the trials, we believe will contribute significantly to the commercial value proposition for Rytelo in the future. Thank you. And we'll now open the line to questions. Operator?

我們堅信，Rytelo 能夠成為這種高端需求、低風險 MDS 治療模式中符合條件的患者護理標準的一部分，並為患者帶來差異化的益處。除了推出低風險 MDS 之外，我們還在推進針對骨髓纖維化的 imetelstat 開發計劃，該試驗取得了積極的成果，我們相信該計劃將在未來為 Rytelo 的商業價值主張做出重大貢獻。謝謝。我們現在開始提問。操作員？

Thank you. (Operator Instructions)

謝謝。（操作員說明）

Tara Bancroft, TD Cowen.

塔拉·班克羅夫特，TD·考恩。

Hi. Good morning, and thanks for taking the questions. So I guess to start, I would love to get a better sense of expectations for the year and what you are targeting. And for that, I know you're probably not providing revenue guidance, but I think it would be helpful to know whether a couple of things, whether you think a J-code could be finalized potentially before January and other metrics, like how soon you think the field team will hit 100% of the target prescriber base? Thanks.

你好。早上好，感謝您提出問題。所以我想首先，我很想更了解今年的期望和目標。為此，我知道您可能不會提供收入指導，但我認為了解一些事情會有所幫助，例如您是否認為 J 代碼可能在一月份之前完成，以及其他指標，例如多快您認為現場團隊將達到100% 的目標處方者基礎嗎？謝謝。

Thanks a lot, Tara. Appreciate the questions, which you're quite correct. We have limited ability to answer six weeks into the launch. I think we're really, really happy with where we've ended up in such a short period of time, and think that that is -- we hope that that's a harbinger of performance as we continue on.

非常感謝，塔拉。感謝您提出的問題，您的回答非常正確。在發布六週後，我們回答的能力有限。我認為我們對在如此短的時間內所取得的成績感到非常非常滿意，並且我們希望這是我們繼續前進的表現的預兆。

I think the J-code, I think we're guiding to the first quarter, because we are honestly not a 100% sure when it will come. History suggests that there is some variability at the end, but we gave that guidance, and I think we'll stick by it for the moment.

我認為 J 代碼，我認為我們正在指導第一季度，因為老實說我們不能 100% 確定它何時到來。歷史表明最終會有一些變化，但我們給了指導，我認為我們暫時會堅持下去。

As we get a little bit closer, we may or may not have more information, but as of the moment, I think we would still stick to the earlier part of the year. I think with regard to metrics on the Salesforce, wow, the Salesforce is completely engaged, as you can imagine.

隨著我們越來越接近，我們可能會也可能不會獲得更多信息，但就目前而言，我認為我們仍然會堅持今年早些時候。我認為關於 Salesforce 上的指標，哇，正如你可以想像的那樣，Salesforce 完全參與其中。

I don't actually have any predictions available to any of us on that, but I do know that they are as -- what's the best word for it? They are as enthusiastic and as hardworking a group of both CAMs, not only the kick-out managers, but also the folks responsible for trade and channel and for all of the various activities involved in a sophisticated commercial launch. I think it's probably all we can say today, but thanks for the question. Look forward to seeing this all evolve over the remainder of the year.

我實際上對此沒有任何可用的預測，但我確實知道它們是——最好的詞是什麼？他們是由兩個 CAM 組成的熱情而勤奮的團隊，不僅是啟動經理，還包括負責貿易和管道以及複雜的商業發布所涉及的所有各種活動的人員。我想這可能就是我們今天能說的全部了，但謝謝你的提問。期待在今年剩餘時間內看到這一切的發展。

Great. Thank you so much.

偉大的。太感謝了。

Carter Gould, Barclays.

卡特·古爾德，巴克萊銀行。

Good morning. Congrats to Chip and team on the early days here. Appreciating that it's early, how would you, I guess that initial 160 patients. Would you characterize that sort of as a bolus or potentially something more sustainable?

早安.祝賀 Chip 和他的團隊早年在這裡。意識到現在還早，你會怎麼樣，我猜最初有 160 名患者。您會將這種藥物描述為丸劑還是可能更永續的藥物？

Again, I appreciate it's early, but would you sort of -- you have a sense that these patients were sort of identified by clinicians ahead of the launch or sort of more spontaneous use? And then on the patent term extension side of things, my understanding as I recall, I think sort of USPTO has, I think, statutorily has like 14 months to respond to your extension.

再說一次，我很高興現在還為時過早，但是您是否有一種感覺，這些患者是在啟動之前被臨床醫生識別出來的，或者是更自發的使用？然後在專利期限延期方面，據我所知，我認為美國專利商標局法定有 14 個月的時間對您的延期做出回應。

Is that correct? And is that a fair characterization of the timeline we should expect to hear back on this front? Thank you.

這是正確的嗎？我們應該期望聽到這方面的回饋，這是對時間表的公平描述嗎？謝謝。

Okay. Thanks Carter. So with regard to the initial uptake and demand and the question of a bolus, you only know a bolus for sure when you see it in the rear view mirror, right. I mean, if the trend line continues, it's not a bolus.

好的。謝謝卡特。因此，關於最初的吸收和需求以及推注的問題，只有當你在後視鏡中看到它時，你才能確定它是推注，對吧。我的意思是，如果趨勢線繼續下去，那麼它就不是一次推注。

If it slacks a bit at some point, I guess you would say it is a bolus. All I can say Carter is, we did not in our own thinking model, we're in a bolus. I think we've been pretty consistent about that and how we've said it. So it's a little hard to know exactly where this will go from here.

如果它在某個時候稍微鬆弛一點，我想你會說它是丸劑。卡特我只能說，我們沒有採取自己的思考模式，我們只是處於一個大團圓之中。我認為我們在這一點以及我們的表達方式上一直非常一致。因此，很難確切地知道接下來會發生什麼。

We do think this is all very indicative of a strong degree of organic demand that really reflects all of the great things that really happened starting with the ODAC, which seems like a million years ago, but it wasn't. And then we got, of course, an excellent, very clean label.

我們確實認為這一切都非常表明了強烈的有機需求，真正反映了從 ODAC 開始真正發生的所有偉大事情，這似乎是一百萬年前，但事實並非如此。當然，我們得到了一個優秀、非常乾淨的標籤。

And then with the NCCN guidelines that really placed this as a forefront of potential standard of care in this space, I think all we can say is we're just seeing a tremendous amount of interest on the part of HCPs, on the part of accounts. And whether this is going to reflect a bolus or not, we don't really know, but I don't think that's something that we've anticipated given the bill and by -- the buying bill nature of the mechanics around all of it.

然後，根據 NCCN 指南，該指南真正將其作為該領域潛在護理標準的前沿，我認為我們只能說，我們只是看到 HCP 和帳戶方面表現出極大的興趣。這是否會反映出推注，我們真的不知道，但我認為考慮到帳單以及圍繞所有這些機制的購買帳單性質，這並不是我們所預期的事情。

With regard to the PTE, I wish it was 14 months, that would be great. I don't know if it's statutorily there or not, I guess it is. But when we've spoken to our IP council and others, we're seeing anywhere from three to five years for the PTO to really get back with definitive, yes, you can apply it to this patent, you can apply it to that patent, etc. So I would not be holding my breath on that.

至於PTE，我希望是14個月，那就太好了。我不知道它是否是法定的，我想是的。但是，當我們與智慧財產權委員會和其他機構交談時，我們看到專利商標局需要三到五年才能真正做出明確的答复，是的，您可以將其應用於該專利，您可以將其應用於該專利等等。

It's out of our hands. We've done everything we can to make these applications, but the historical performance has been pretty slow.

它不在我們手中。我們已盡一切努力來製作這些應用程序，但歷史性能相當緩慢。

Understood. Thank you.

明白了。謝謝。

Stephen Willey, Stifel.

史蒂芬威利，斯蒂菲爾。

Yes. Good morning. Thanks for taking the question and congrats on the progress. I appreciate some of the early metrics here, but just curious, of the 160 patients that have started therapy, can you comment as to how many of those patients are actually paying per drug? Is there a yet to be worked out reimbursement process for some of these patients?

是的。早安.感謝您提出問題並祝賀取得的進展。我很欣賞這裡的一些早期指標，但只是好奇，在 160 名已開始治療的患者中，您能否評論一下其中有多少患者實際上為每種藥物付費？對於其中一些患者是否有尚未制定的報銷流程？

I think I'm going to let probably either Andy or Michelle take that. I have a few comments, but they may be in a better position to answer that question. Andy, do you have any thoughts about that?

我想我會讓安迪或米歇爾接受這個。我有一些評論，但他們可能更適合回答這個問題。安迪，你對此有什麼想法嗎？

I think its way early Chip to know. Although, what we do know is that we haven't had any issues with any of the submissions that have been made to-date. These patients have just gone through their first cycle.

我認為奇普很早就知道了。儘管如此，我們所知道的是，迄今為止提交的任何內容都沒有任何問題。這些患者剛剛經歷了第一個週期。

Yes. I mean, I guess I would add that, again, as Andy said, we haven't received any pushback. We have a hub set up, a reimbursement process. Even with the temporary J-code, customers are pushing this through formularies and so reimbursement has not been an issue so far.

是的。我的意思是，我想我要補充一點，正如安迪所說，我們沒有收到任何阻力。我們建立了一個中心，一個報銷流程。即使使用臨時 J 代碼，客戶也會透過處方集推動這一點，因此到目前為止報銷還不是問題。

Steve, I guess the only other comment I would have, which may or may not be helpful in this regard, remember everyone, this is predominantly a Medicare population. And while we don't have as fine insight into the exact breakdowns of where reimbursement is coming from, we know that the majority of it is PHS.

史蒂夫，我想我唯一的其他評論可能在這方面有幫助也可能沒有幫助，請記住每個人，這主要是醫療保險人群。雖然我們對報銷來源的具體細節沒有那麼深入的了解，但我們知道其中大部分是 PHS。

And that's historically not had a lot of pushback, as long as you have the NCCN guidelines where they are today for us in Category 1, Category 2A. So again, the early days, we may be able to give a little bit more insight into this, but I think the current situation as we see it, bodes well for the future.

從歷史上看，只要您有 NCCN 指南（我們今天的指南屬於第 1 類、第 2A 類），這一點就不會遇到太多阻力。因此，在早期，我們也許能夠對此有更多的了解，但我認為我們所看到的當前情況預示著未來的好兆頭。

Understood. And again, I guess, understanding that it's early, but do you have any early information on just whether or not you are seeing patients who are newly starting Rytelo being switched off of other salvaged therapy? And I guess in your conversation with physicians, is that a dynamic that you expect to play out as the launch proceeds?

明白了。再說一次，我想，理解現在還為時過早，但是您是否有任何早期資訊來說明您是否看到新開始 Rytelo 的患者正在停止使用其他挽救療法？我想在您與醫生的對話中，您希望隨著發布的進行而出現這種動態嗎？

Yes, I'll take that. And then I'll invite my colleagues to make any additional comments, if any. Look, I think we just naturally expect some of these patients will be, as you said, patients from the third line if you will, or second or third line for sure. That would be natural in the availability of a new agent and so forth.

是的，我會接受的。然後我將邀請我的同事提出任何其他意見（如果有）。聽著，我認為我們自然期望這些患者中的一些患者將是，正如您所說，如果您願意的話，來自第三線的患者，或者肯定是第二線或第三線的患者。這在新代理人的可用性等方面是很自然的。

But we don't really have a way to characterize that. Our information that comes to us on individual patient data is very limited, extremely limited, if any at all. We're really seeing the demand from accounts flowing into the specialty distributors and occasionally to a specialty pharmacy. And that's what we're really able to infer and figure out the dynamics on.

但我們確實沒有辦法來描述這一點。我們獲得的有關個別患者數據的資訊非常有限，極其有限（如果有的話）。我們確實看到客戶的需求流入專業經銷商，偶爾也流入專業藥局。這就是我們真正能夠推斷和弄清楚動態的東西。

I'm not sure when and exactly how much fine tooth detail we're going to get on individual patients. I think that's going to take some more anecdotal information and eventually perhaps even some studies or whatever. I don't want to promise anything here. Of course, we're deeply interested in knowing the answers to all of that.

我不確定我們何時以及具體會在個別患者身上獲得多少精細的牙齒細節。我認為這將需要更多的軼事信息，最終甚至可能需要一些研究或其他什麼。我不想在這裡承諾任何事情。當然，我們非常想知道所有這些問題的答案。

But six weeks in, I can tell you right now Steve, we're just not really 100% sure exactly the circumstances of these patients and exactly the buckets as it were, that they are coming out of. We're just grateful that they are there.

但六週後，我現在可以告訴你，史蒂夫，我們並不能真正 100% 確定這些患者的具體情況以及他們即將走出的困境。我們很感激他們在那裡。

Understood. And then maybe just one quick question for Faye. Can you just remind us what the DLT window in the IMproveMF trial is? And for a patient who progresses on frontline rocks, are the next-gen jack inhibitors allowed in best available therapy?

明白了。然後也許只是問費耶一個簡單的問題。您能否提醒我們 IMproveMF 試驗中的 DLT 視窗是什麼？對於在前線岩石上取得進展的患者，最佳可用療法是否允許使用下一代傑克抑制劑？

Hi. So the first question is about IMproveMF, correct?

你好。所以第一個問題是關於 IMproveMF，對嗎？

Correct.

正確的。

DLT window, I'm not -- the cycle length is 28 days, and the DLT window is one cycle length. And the next question was about MYF3001 or is whether next-gen --

DLT 窗口，我不是——週期長度是 28 天，DLT 窗口是一個週期長度。下一個問題是關於 MYF3001 或下一代——

Whether the next-gen jack inhibitors are allowable therapy in the best available therapy control arm.

下一代傑克抑制劑是否是最佳可用治療控制臂中允許的治療方法。

No. There are no jack inhibitors allowed on the BAP arm.

不。BAP 臂上不允許使用千斤頂抑制器。

Okay. Thank you very much for taking the questions.

好的。非常感謝您接受提問。

Thanks, Steve.

謝謝，史蒂夫。

Corinne Johnson, Goldman Sachs.

科琳·約翰遜，高盛。

Hey, good morning, guys. Maybe if you could just help us think directionally about the trajectory of new patient growth from here, probably through like the early launch period. Do you anticipate that kind of the new patients coming on therapy will come at a relatively steady clip, that it could be more lumpy or that it would accelerate over time? And maybe precedent would be helpful as you think about the answer there.

嘿，早上好，夥計們。也許您能幫助我們從現在開始定向思考新患者的成長軌跡，可能會經歷早期啟動階段。您是否預期接受治療的新患者會以相對穩定的速度出現，可能會更加不穩定，還是會隨著時間的推移而加速？當你思考答案時，也許先例會有所幫助。

And then in terms of just target engagement, you mentioned obviously 60% of the top decile accounts. I guess how many patients on average are like from a range, are these accounts treating, and of that what portion would be eligible for Rytelo? Thanks.

然後就目標參與度而言，您顯然提到了 60% 的前十分之一帳戶。我猜想平均有多少患者來自某個範圍，這些帳戶正在接受治療，其中哪一部分有資格接受 Rytelo？謝謝。

I'll take the first one, which is the directionality, and as you said, the smoothness versus the lumpiness. I mean, I'm going to say the obvious, Corinne, so forgive me. This is only the second new product launch in the last, what, 12 years in low-risk MDS or maybe there's been a few others that they have been very modest launches. And so all we really -- we don't have a lot to go on on this and six weeks isn't very much.

我將採取第一個，即方向性，正如你所說，平滑度與塊度。我的意思是，我要說的是顯而易見的事情，科琳，所以請原諒我。這只是過去 12 年來針對低風險 MDS 推出的第二個新產品，或者可能還有其他一些新產品的推出非常溫和。所以我們真的——我們在這件事上沒有太多可做的，六週的時間也不算長。

I will say that maybe something that might be helpful is that we haven't seen a particularly, so far in all of six weeks, we haven't seen a particularly lumpy accretion of patients. It's been pretty steady, but it's hard to do a trend line based on that. Maybe then next time we talk, we'll have a better feel for that. But I don't see any particular reason other than just natural variation as things go on, that we would expect anything different than what we've seen to date, but don't really know.

我想說的是，也許可能有幫助的是，到目前為止，在六週的時間裡，我們還沒有看到特別腫塊狀的病人堆積。它相當穩定，但很難以此為基礎繪製趨勢線。也許下次我們談話時，我們會有更好的感覺。但除了隨著事情的發展而自然變化之外，我沒有看到任何特殊的原因，我們會期待任何與我們迄今為止所看到的不同的東西，但並不真正知道。

In terms of target engagement, just a couple of comments about this. These accounts are a very wide variety of accounts. So some accounts are large hospital systems. Some accounts are individual practitioners, everything in between you can imagine.

就目標參與度而言，對此僅作幾點評論。這些帳戶的種類非常廣泛。所以有些帳戶是大型醫院系統。有些帳戶是個人從業者，介於兩者之間的一切你都可以想像。

The top deciles tend to be larger aggregator accounts, many, many physicians. So I don't have an exact number of physicians, but I'm not sure how helpful it would be, because it is such a wide variety. What we do know is that we've had really good traction getting in. We've had excellent traction speaking to these accounts in person, and the number of accounts touched and reached and including the vast majority in person is growing every day.

前十分之一往往是較大的聚合帳戶，有很多很多醫生。所以我沒有確切的醫生數量，但我不確定這會有多大幫助，因為種類繁多。我們所知道的是，我們的市場吸引力非常大。我們親自與這些客戶交談時獲得了極大的吸引力，接觸和接觸的客戶數量（其中絕大多數是面對面的）每天都在增長。

So Andy, again, I don't know if you have any insight into this, but I will invite any help we can give Corrine here.

所以安迪，再次，我不知道你對此是否有任何見解，但我會邀請我們可以在這裡為科林提供任何幫助。

Nope. I think that's it, Chip. Yeah, I mean, account activation is accelerating, we believe that, so we're pretty pleased so far. And the top deciles, we obviously modeled based on flow of prior treatments when they went for that launch.

沒有。我想就是這樣，奇普。是的，我的意思是，帳戶啟動正在加速，我們相信這一點，所以到目前為止我們非常高興。對於前十分之一，我們顯然是根據他們進行該發佈時的先前治療流程進行建模的。

But I don't know that it's more proportionality. I don't think we can give patient numbers per account right now.

但我不知道這是否更相稱。我認為我們現在無法提供每個帳戶的患者人數。

Okay. Thank you.

好的。謝謝。

Gil Blum, Needham & Company.

吉爾布魯姆，李約瑟公司。

Hey. Good morning everyone and thanks for including our questions. So I know this is very early, but is there any information you can provide about the split of these patients that were dose RS positive, RS negative, front line, second line, whichever information you have. Thank you.

嘿。大家早安，感謝您提出我們的問題。所以我知道這還為時過早，但是您是否可以提供有關這些劑量 RS 陽性、RS 陰性、前線、二線患者的劃分的任何信息，無論您有什麼信息。謝謝。

Yeah. Thanks, Gil. Thanks for the question. We don't have it.

是的。謝謝，吉爾。謝謝你的提問。我們沒有。

It's not the kind of information that would come in at this moment in time. We get, this is pretty much demand information that we're able to give you. This is the number of vials going out the door. And what we eventually, I think we will try very hard to get that.

這不是此時此刻會出現的訊息。我們知道，這幾乎是我們能夠為您提供的需求資訊。這是出廠的小瓶數量。我認為我們最終會非常努力地實現這一目標。

We're as interested as anybody in the nuances of, again, which buckets these patients are coming out. But as of today, no, we don't have that, and it will take some tweaking of our information sources and how we get that over the next several, I would think many quarters perhaps, to actually get a really accurate view on that. But as of today, we just don't know.

我們和任何人一樣對這些患者的細微差別感興趣。但截至今天，不，我們還沒有這樣的信息，需要對我們的信息來源以及我們如何在接下來的幾個季度（我想可能是很多季度）中獲得這些信息進行一些調整，才能真正獲得真正準確的看法。但截至今天，我們還不知道。

Thanks, Chip. That's very helpful.

謝謝，奇普。這非常有幫助。

Sure.

當然。

And another question and then a kind of related one. How long do you think it would take until you start getting feedback from treating physicians as it relates to any challenges they are having at giving the drug or any other kind of bottlenecks? Thank you.

還有另一個問題，然後是相關的問題。您認為需要多長時間才能開始從治療醫生那裡獲得回饋，因為這與他們在給予藥物時遇到的任何挑戰或任何其他類型的瓶頸有關？謝謝。

Yes. Thanks. Well, I think that boils down to the people that we have deployed in the field. Again, I didn't invite Andy to comment about that, because if you remember that slide that he showed, we've got a really varied group of people out in the field, and I feel quite good about that.

是的。謝謝。嗯，我認為這可以歸結為我們在該領域部署的人員。再說一次，我沒有邀請安迪對此發表評論，因為如果你還記得他展示的那張幻燈片，我們在這個領域有一群非常不同的人，我對此感覺很好。

But Andy, you might want to just run through sort of how we get feedback.

但是安迪，您可能只想了解我們如何獲得回饋。

Sure. Yes. I mean, we have several channels obviously, but I think our med affairs team that's in the field and our Medical Affairs Hub, which is fully active, is right now probably the main source of flow of certainly information requests. I think its way early to start getting specific feedback.

當然。是的。我的意思是，我們顯然有幾個管道，但我認為我們在現場的醫療事務團隊和我們完全活躍的醫療事務中心現在可能是特定資訊請求流的主要來源。我認為現在開始獲得具體回饋還為時過早。

Again, given that we're only six weeks in, most of these patients are just through a single cycle of treatment. But we have seen a strong, and I think a strong volume of med info requests across a range of different areas, from efficacy and safety to dosing and reactions to the prescribing information. So I think that bodes well that physicians are interested and becoming more and more educated about treating with Rytelo.

同樣，考慮到我們只有六週的時間，大多數患者剛完成一個治療週期。但我們看到了來自各個不同領域的強烈的、我認為大量的醫療資訊請求，從功效和安全性到劑量和對處方資訊的反應。因此，我認為這是一個好兆頭，醫生們對 Rytelo 治療很感興趣，並且越來越了解 Rytelo 治療。

All right. Thanks for taking our questions and congrats on the launch.

好的。感謝您提出問題並祝賀我們的發布。

Kalpit Patel, B. Riley Securities.

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

Yes. Hey, good morning and thanks for taking the question. For the launch, I guess, do you have an early estimate or early sense of what the growth net adjustments would be for third quarter and how you anticipate that to shift over time, maybe into fourth quarter or early 2025?

是的。嘿，早上好，感謝您提出問題。對於此次發布，我想，您是否對第三季度的增長淨調整有一個早期的估計或早期的感覺，以及您預計隨著時間的推移，可能會進入第四季度或2025 年初，這種情況將如何變化？

I appreciate your question. I think Michelle's probably the best person to answer that question. Michelle?

我很欣賞你的問題。我認為米歇爾可能是回答這個問題的最佳人選。米歇爾？

Yes. Thanks, Kalpit. I mean, we obviously only had one week for the June close and our growth to net calculation, so. I mean, it's a pretty straightforward growth to net breakdown of components.

是的。謝謝，卡爾皮特。我的意思是，我們顯然只有一周的時間來計算六月的收盤價和我們的淨增長，所以。我的意思是，組件淨細分的成長非常簡單。

I mean, because it is a primary Medicare population. So we know the PHS is going to be one of our largest deductions in the growth to net. But I would say it's too early for us to really be comfortable and we need more data as the July sales close out and as well as the rest of the quarter, but we'll have a pretty good sense after a full quarter worth of sales.

我的意思是，因為這是主要的醫療保險人口。因此，我們知道 PHS 將成為我們淨成長中最大的扣除項目之一。但我想說，現在要真正感到舒適還為時過早，隨著7 月銷售結束以及本季度剩餘時間的結束，我們需要更多數據，但在整個季度的銷售量之後我們會有一個很好的感覺。

OK. OK and as a follow-up, how are you viewing the current sell side consensus estimates for Rytelo in the second half of this year under your current launch projections?

好的。好的，作為後續行動，根據您目前的發布預測，您如何看待今年下半年 Rytelo 目前的賣方共識估計？

Michelle?

米歇爾？

So I would say from a consensus perspective, as I mentioned before, I think that we need to sort of sit down with you guys and go through some of the assumptions, because they are definitely mixed among the different models and sort of mixed versus our internal models.

所以我想說，從共識的角度來看，正如我之前提到的，我認為我們需要與你們坐下來討論一些假設，因為它們肯定混合在不同的模型中，並且與我們的模型不同。 。

And I think it's a lot on the annual cost per patient. There's a lot of variance between the models there, so which I think is probably contributing to that, would be duration of therapy and penetration is pretty varied. So I think that we'll look to give guidance on that post this earnings call.

我認為每個患者每年的費用很高。那裡的模型之間存在很大差異，因此我認為這可能是造成這種情況的原因，治療持續時間和滲透力差異很大。因此，我認為我們將在本次財報電話會議上提供指導。

Okay. And then one last one on the NCCN guidelines. I guess, were there any surprises based on where imetelstat is positioned in all the different subgroups of the treatment algorithm? And do your internal estimates of the percentage of lower MDS patients that could be treated with Rytelo change based on this position?

好的。然後是 NCCN 指南的最後一項。我想，根據 imetelstat 在治療演算法的所有不同子組中的位置，是否有任何驚喜？您對可以接受 Rytelo 治療的低度 MDS 患者百分比的內部估計是否會根據這一立場而改變？

Yes. I'll take that one. And then if Faye listens in and has anything else to contribute, I'd encourage her to do it. It's a great question, Kal.

是的。我會接受那個。然後，如果 Faye 傾聽並有任何其他貢獻，我會鼓勵她這樣做。這是一個很好的問題，卡爾。

So first of all, I think if you go back to, all the way back to top-line results, you know what, close to a year and a half to two years ago, we identified at that point in time a couple of really big pockets of value here. The first one was of course, that we thought that we were effective regardless of our status, and so in both, the RS positive and the RS negative.

首先，我認為如果你回顧一下，一直回到頂線結果，你知道嗎，大約一年半到兩年前，我們當時確定了一些真正的結果這裡有大量的價值。第一個當然是，我們認為無論我們的狀態如何，我們都是有效的，因此無論是 RS 積極還是 RS 消極。

Second of all, we did have enough patients, although not a ton of luspatercept patients previously treated. And as we used to say, that was a highlight of the previous year's ASH that we saw some really good results there.

其次，我們確實有足夠的患者，儘管之前接受過治療的 luspatercept 患者並不多。正如我們過去常說的，這是去年 ASH 的一個亮點，我們在那裡看到了一些非常好的結果。

So we thought that previously treated luspatercept patients who were not doing as well as physicians would likely be important. We thought that the high transfusion burden patients would be very attractive. And then we also identified that it looks like the patients who had serum EPO levels greater than 500, that is the officially the ESA and eligible patients had done pretty well. And so, we actually saw from our Phase 3 results, pretty much the makings of where we ended up today.

因此，我們認為以前接受過 luspatercept 治療但表現不如醫生的患者可能很重要。我們認為高輸血負擔的患者會很有吸引力。然後我們還發現，看起來血清 EPO 水平大於 500 的患者，這是 ESA 的官方數據，符合條件的患者表現得相當不錯。因此，我們實際上從第三階段的結果中看到了我們今天的結果。

What I can say is the label, which of course did have some transfusion burden requirements on it, as you would expect based on the clinical trial, that didn't actually translate over to the NCCN guidelines, which is interesting, frequently is not the case in as NCCN looks at treatment algorithms, if you will.

我能說的是，標籤上當然有一些輸血負擔要求，正如您根據臨床試驗所期望的那樣，這實際上並沒有轉化為 NCCN 指南，這很有趣，通常不是如果你願意的話，請以NCCN 研究治療演算法為例。

And then all the other pockets really are completely there. So I have to say, I don't think we -- what the pleasant surprise was, that there were no unpleasant surprises. I think we just got a wonderful NCCN guideline affirmation of what we've always seen as the value in these various different areas.

然後所有其他口袋就真的完全在那裡了。所以我必須說，我不認為我們——令人愉快的驚喜是什麼，也沒有不愉快的驚喜。我認為我們剛剛得到了一個精彩的 NCCN 指南，肯定了我們一直認為這些不同領域的價值。

So I don't think that -- I think it's pretty much what we were hoping for and what we had always imagined. So, Faye, I don't know if you have any other comments about it. Great question though.

所以我不認為——我認為這幾乎是我們所希望的和我們一直想像的。那麼，Faye，我不知道你對此還有什麼其他評論嗎？不過，這是一個很好的問題。

Well, yes. Chip, I think you put it well. I think the only surprise was the pleasant one. We received everything that we were asking for and their strong Category 1 and 2A guidelines and a strong reflection of the data of the clinical trial. So all-in-all, a good result.

嗯，是的。奇普，我認為你說得很好。我認為唯一的驚喜是令人愉快的。我們收到了我們所要求的一切，以及他們強有力的 1 類和 2A 類指南以​​及對臨床試驗數據的強烈反映。所以總而言之，這是一個很好的結果。

Okay. Thanks very much for taking the questions.

好的。非常感謝您提出問題。

This concludes the question-and-answer session. I'll turn the call to Aron for closing remarks.

問答環節到此結束。我將把電話轉給阿倫，讓他致閉幕詞。

Thank you so much for joining us today. We appreciate your interest in Geron and look forward to keeping you updated during this very exciting time for our company. Goodbye.

非常感謝您今天加入我們。我們感謝您對 Geron 的興趣，並期待在我們公司這個令人興奮的時刻為您提供最新資訊。再見。

This concludes today's conference call. We thank you for joining. You may now disconnect.

今天的電話會議到此結束。我們感謝您的加入。您現在可以斷開連線。