Geron Corp (GERN) 2023 Q2 法說會逐字稿

Good afternoon, everyone. Welcome to the Geron Corporation Second Quarter 2023 Earnings Conference Call. I am Aron Feingold, Geron's Vice President of Investor Relations and Corporate Communications. I'm joined today by several members of Geron's management team. Dr. John Scarlett, Chairman and Chief Executive Officer; Olivia Bloom, Executive Vice President and Chief Financial Officer; Dr. Faye Feller, Executive Vice President and Chief Medical Officer; Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer; and Dr. Andrew Grethlein, Executive Vice President and Chief Operating Officer.

大家下午好。歡迎參加 Geron Corporation 2023 年第二季財報電話會議。我是 Aron Feingold，Geron 的投資者關係和企業傳播副總裁。今天，Geron 管理團隊的幾位成員也加入了我的行列。約翰‧史嘉莉博士，董事長兼執行長；奧莉維亞·布魯姆（Olivia Bloom），執行副總裁兼財務長； Faye Feller 博士，執行副總裁兼首席醫療官； Anil Kapur，企業策略執行副總裁兼首席商務長；執行副總裁兼營運長 Andrew Grethlein 博士。

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 therapeutic potential and potential regulatory approval of imetelstat, anticipated clinical and commercial events and related timelines, the sufficiency of Geron's financial resources and other statements that are not historical facts. Actual events or results could differ materially.

在我們開始之前，請注意，在本次演示和問答環節中，我們將就未來事件、業績、計劃、期望和其他預測（包括與治療潛力和潛力相關的預測）做出前瞻性陳述。監管批准、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。實際事件或結果可能有重大差異。

Therefore, I refer you to the discussion under the heading Risk Factors in Geron's Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, 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.

因此，我建議您參閱Geron 截至2023 年6 月30 日的季度表10-Q 季度報告中風險因素標題下的討論，其中確定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 afternoon, everyone. Thanks for joining us today. Geron's most recent quarter was punctuated by important achievements, which support our evolution from a late-stage clinical development company toward one with future substantial commercial capabilities.

謝謝，阿倫。大家下午好。感謝您今天加入我們。 Geron 最近一個季度取得了一些重要成就，這些成就支持我們從一家後期臨床開發公司發展成為未來具有強大商業能力的公司。

Foremost among these achievements was the submission in mid-June of a new drug application for imetelstat in lower-risk MDS. This was the first NDA ever submitted for a telomerase inhibitor and reflects our team's dedication, commitment and focus on groundbreaking and innovative drug development over many years. Other important milestones included presentations at both ASCO and EHA of new data and analyses from the IMerge Phase III lower-risk MDS trial.

這些成就中最重要的是於 6 月中旬提交了治療低風險 MDS 的新藥 imetelstat 申請。這是有史以​​來提交的第一份端粒酶抑制劑 NDA，反映了我們團隊多年來對突破性和創新藥物開發的奉獻、承諾和關注。其他重要的里程碑包括在 ASCO 和 EHA 上介紹 IMerge III 期低風險 MDS 試驗的新數據和分析。

These data contributed to the evidence for compelling imetelstat efficacy profile, including durable continuous transfusion independence as well as substantial increases in serum hemoglobin. Broad responses across MDS subtypes including in ring sideroblast positive and negative patients as well as in high-transfusion-burdened patients were also reported. Further, the presentations reflected strong evidence for potential disease-modifying activity as well as patient-reported outcomes have improved fatigue in imetelstat-treated patients. Faye will comment in more detail on these clinical data updates later on this call.

這些數據為伊美司他功效提供了令人信服的證據，包括持久的連續輸血獨立性以及血清血紅蛋白的大幅增加。也報告了跨 MDS 亞型的廣泛反應，包括環形鐵粒幼細胞陽性和陰性患者以及高輸血負擔患者。此外，這些演示反映了潛在的疾病緩解活性的有力證據，以及患者報告的結果改善了伊美司他治療患者的疲勞狀況。 Faye 稍後將在本次電話會議上更詳細地評論這些臨床數據更新。

Collectively, these data distinguish imetelstat from other treatments for patients with lower-risk MDS that are available commercially or that are in development today. Based on our market research, including perspectives gained from both academic and community hematologists, we believe the broad hematology community considers imetelstat an important potential treatment option for patients with lower-risk MDS.

總的來說，這些數據將 imetelstat 與其他針對低風險 MDS 患者的治療方法區分開來，這些治療方法已商業化或目前正在開發中。根據我們的市場研究，包括學術界和社區血液學家的觀點，我們相信廣大血液學界認為伊美司他是低風險 MDS 患者的重要潛在治療選擇。

Our market insights show that imetelstat is positioned to become a new standard of care in lower-risk MDS, particularly for difficult-to-treat subgroups who have very limited options today. As a result, we believe the total addressable market in lower-risk MDS for imetelstat is approximately $3.5 billion in 2033. In order to execute on that large of an opportunity, we're in a full-court press to push forward our launch readiness and expect to be ready for a U.S. commercial launch upon potential approval in early 2024. Anil will reprise the latest imetelstat market research in lower-risk MDS and launch readiness update in more detail later on this call today.

我們的市場洞察表明，imetelstat 有望成為低風險 MDS 的新治療標準，特別是對於目前選擇非常有限的難治亞群。因此，我們相信到 2033 年，imetelstat 的低風險 MDS 的潛在市場總額約為 35 億美元。在美國進行商業發布。

Another important element of Geron's value proposition is IMpactMF, our pivotal trial evaluating imetelstat in myelofibrosis patients who are relapsed or refractory to JAK-inhibitors. This is the only Phase III clinical trial in myelofibrosis using overall survival as a primary endpoint. We believe a positive outcome could transform the treatment landscape for these MF patients who have limited treatment options and a dismal survival outlook.

Geron 價值主張的另一個重要元素是 IMpactMF，這是我們評估 imetelstat 對 JAK 抑制劑復發或難治性骨髓纖維化患者的關鍵試驗。這是唯一一項以總存活期作為主要終點的骨髓纖維化 III 期臨床試驗。我們相信，積極的結果可能會改變這些治療選擇有限且生存前景黯淡的 MF 患者的治療前景。

Faye will be providing further detail on enrollment in the IMpactMF trial later on the call. Based on our current planning assumptions for both enrollment and death rates in the trial, today we're updating our guidance for the interim analysis to be expected in the first half of 2025 and for the final analysis to be expected in the first half of 2026. From a financial resource perspective, we have approximately $400 million on the balance sheet as of the second quarter close. This gives us the financial wherewithal to fund a potential successful launch in lower-risk MDS and also to support operations through the first year of launch. Olivia will comment during the call on the status of warrant exercises and our expectations regarding our cash runway based on these current financial resources.

Faye 將在稍後的電話會議上提供有關 IMpactMF 試驗註冊的更多詳細資訊。根據我們目前對試驗中入組率和死亡率的規劃假設，今天我們正在更新預計在 2025 年上半年進行的中期分析和預計在 2026 年上半年進行的最終分析的指南從財務資源的角度來看，截至第二季末，我們的資產負債表上約有4 億美元。這為我們提供了資金，可以為低風險 MDS 的潛在成功啟動提供資金，並支持啟動第一年的營運。奧莉維亞將在電話會議上評論認股權證行使的狀況以及我們根據當前財務資源對現金跑道的預期。

Before I turn this call over to Faye, I'm very pleased to announce today the appointment of Scott Samuels as Geron's new Chief Legal Officer, following Stephen Rosenfield's retirement at the beginning of this month. Stephen's been the Chief Legal Officer of Geron since shortly after I came to the company more than a decade ago and both I and the Board are deeply grateful for Stephen's partnership and contributions to Geron since then. I'm personally very pleased for Stephen that he'll now be able to enjoy his much-deserved retirement.

在我把這通電話轉給 Faye 之前，我很高興今天宣布任命 Scott Samuels 為 Geron 的新首席法律官，繼 Stephen Rosenfield 本月初退休後。十多年前，我來到 Geron 公司後不久，Stephen 就擔任了 Geron 的首席法務官，我和董事會都對 Stephen 自此以來的合作夥伴關係和對 Geron 做出的貢獻深表感謝。我個人為史蒂芬感到非常高興，因為他現在能夠享受他應得的退休生活。

Prior to joining Geron as our new Executive Vice President, Chief Legal Officer and Corporate Secretary, Scott Samuels recently served as the General Counsel of BeiGene, where he built a large global legal and compliance team, oversaw launches of 3 internally developed drug products in the U.S., Europe and China, developed a global health care compliance program and led key strategic transactions with Amgen, Novartis and Celgene, which, of course, is now BMS. Prior to BeiGene, Scott was the Assistant General Counsel and then an Acting General Counsel at ARIAD, where he managed the company's legal affairs, including SEC compliance and corporate governance and key licensing and distribution agreements prior to ARIAD's acquisition by Takeda. I believe Scott's experience, technical expertise and history of success in building legal and compliance organizations to meet the needs of a commercial company epitomizes what our current and our many new employees are focused on as we pursue the future evolution and growth of Geron. Both the Board and I greatly look forward to working with Scott.

在加入Geron 擔任新任執行副總裁、首席法務官兼公司秘書之前，Scott Samuels 最近擔任百濟神州的總法律顧問，他在那裡建立了一個大型的全球法律和合規團隊，監督了3 種內部開發的藥品在全球的上市。 (BMS)）的關鍵策略交易。在加入百濟神州之前，Scott 曾擔任ARIAD 的助理總法律顧問，然後擔任代理總法律顧問，負責管理公司的法律事務，包括SEC 合規性和公司治理以及ARIAD 被武田收購之前的關鍵許可和分銷協定.我相信 Scott 在建立法律和合規組織以滿足商業公司的需求方面的經驗、技術專長和成功歷史集中體現了我們當前和許多新員工在追求 Geron 未來發展和成長時所關注的重點。董事會和我都非常期待與斯科特合作。

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

這樣，我會將電話轉給 Faye，以了解監管和臨床開發的最新情況。菲？

Thank you, Chip, and good afternoon to everyone on the call. As Chip mentioned, we are thrilled to have submitted our imetelstat new drug application in June 2023 for the treatment of transfusion-dependent anemia in adult patients with low to intermediate one-risk MDS who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agent or ESA.

謝謝你，奇普，祝所有參加電話會議的人下午好。正如Chip 所提到的，我們很高興於2023 年6 月提交了imetelstat 新藥申請，用於治療患有低至中度單危MDS 的成人患者的輸血依賴性貧血，這些患者對治療無反應或失去反應或不符合資格用於紅血球生成刺激劑或 ESA。

As permitted under imetelstat Fast Track designation, we have requested that the FDA grant priority review of the NDA. We expect FDA will communicate potential acceptance of the NDA within 60 days of submission, that is sometime in mid-August and reveal the PDUFA date for such a review. Under a priority review scenario, we would expect potential NDA approval timing in the first quarter of next year.

根據 imetelstat 快速通道指定的允許，我們已請求 FDA 對 NDA 進行優先審查。我們預計 FDA 將在提交後 60 天內（即 8 月中旬的某個時間）傳達可能接受 NDA 的訊息，並公佈此類審查的 PDUFA 日期。在優先審查的情況下，我們預計新藥申請的批准時間可能在明年第一季。

Under standard of review, we would expect potential approval timing in the second quarter of 2024. To expand imetelstat's potential reach outside of the U.S., we remain on track to submit a marketing authorization application in the European Union for lower-risk MDS in the fourth quarter of 2023. As we await potential commercialization in the U.S., we initiated an expanded access program, or EAP, in June 2023.

根據審查標準，我們預計可能會在 2024 年第二季獲得批准。季度。

This is a program that enables us to make imetelstat available to clinicians and patients prior to FDA approval. Treatment of lower-risk MDS patients in this program is based on the protocol approved by FDA, which requires each treating physician to apply for access for their patients. We have heard physicians in both academic and community settings express the need for new treatment options for their lower-risk MDS patients and we are pleased to be able to offer this expanded access program to the low-risk MDS community.

該計劃使我們能夠在 FDA 批准之前向臨床醫生和患者提供 imetelstat。該計劃中低風險 MDS 患者的治療基於 FDA 批准的方案，該方案要求每位治療醫生為其患者申請訪問權限。我們聽到學術界和社區的醫生表示需要為低風險 MDS 患者提供新的治療選擇，我們很高興能夠向低風險 MDS 社區提供這項擴大的准入計劃。

Patients treated with imetelstat in the expanded access program are expected to ultimately be transitioned to commercial supply within 3 months after a potential future FDA approval of the drug. As Chip described, at ASCO and EHA, we presented new data and analyses from IMerge. These data further differentiate imetelstat from existing treatments and support its role as a potential new standard of care in lower-risk MDS.

在擴大准入計畫中接受 imetelstat 治療的患者預計在 FDA 未來可能批准該藥物後 3 個月內最終過渡到商業供應。正如 Chip 所描述的，我們在 ASCO 和 EHA 上展示了來自 IMerge 的新數據和分析。這些數據進一步將 imetelstat 與現有治療方法區分開來，並支持其作為低風險 MDS 潛在新護理標準的作用。

The content of these presentations were also reported on June 14 during the Geron-hosted investor event. We encourage investors to access the archived webcast, which is available on the Investor portion of our website under Events. There, you can hear hematologic malignancy key opinion leaders and IMerge investigators, Dr. Uwe Platzbecker and Rami Komrokji, present these data in detail.

這些演講的內容也在 6 月 14 日由 Geron 主辦的投資者活動期間進行了報告。我們鼓勵投資者訪問存檔的網路廣播，該網路廣播可在我們網站的「投資者」部分的「活動」下找到。在那裡，您可以聽到血液惡性腫瘤關鍵意見領袖和 IMerge 研究者 Uwe Platzbecker 博士和 Rami Komrokji 詳細介紹這些數據。

For the purposes of our call today, I will provide an overview of the key points of imetelstat differentiation highlighted in our ASCO and EHA presentation. First, the clinically meaningful and durable transfusion independence or TI experienced by imetelstat-treated patients in IMerge is unprecedented for patients with lower-risk MDS. We observed a highly statistically significant improvement in TI rates in imetelstat-treated patients for 8-week, 16-week and 24-week TI compared with placebo.

為了今天的電話會議，我將概述 ASCO 和 EHA 演講中強調的 imetelstat 差異化要點。首先，IMerge 中接受 imetelstat 治療的患者所經歷的具有臨床意義和持久的輸血獨立性或 TI 對於低風險 MDS 患者來說是前所未有的。我們觀察到，與安慰劑相比，伊美司他治療的患者 8 週、16 週和 24 週 TI 的 TI 率有高度統計學顯著性改善。

Even more exciting with 3 months of additional follow-up, nearly 20% of the imetelstat-treated patients experienced a 1-year TI, which represents approximately 60% of imetelstat 24-week responders. Additionally, heme malignancy KOLs at ASCO and EHA noted the statistically significant improvement of anemia with a median hemoglobin rise of 3.6 grams per deciliter for imetelstat-treated 8-week TI responders as a very important point of differentiation.

更令人興奮的是，經過 3 個月的額外隨訪，近 20% 的 imetelstat 治療患者經歷了 1 年 TI，相當於 imetelstat 24 週緩解者的約 60%。此外，ASCO 和EHA 的血紅素惡性腫瘤KOL 指出，對於接受imetelstat 治療的8 週TI 應答者來說，貧血有統計學上的顯著改善，中位血紅蛋白升高了3.6 克/分升，這是一個非常重要的區分點。

Second, a breadth of clinically meaningful responses was observed across key MDS subgroups, including difficult-to-treat populations such as those without ring sideroblast or Rh-negative patients as well as high transfusion burden patients and those with high serum EPO levels. These patient populations have not been studied with most other agents used to treat the anemia of lower-risk MDS nor have such results been seen with other treatments.

其次，在MDS關鍵亞組中觀察到了廣泛的具有臨床意義的反應，包括難以治療的人群，例如沒有環形鐵粒幼細胞或Rh陰性患者，以及高輸血負擔患者和血清EPO水平高的患者。這些患者群體尚未與用於治療低風險 MDS 貧血的大多數其他藥物一起進行研究，也未在其他治療中看到這樣的結果。

At EHA, we presented important new subgroup analysis showing that the rate and durability of TI, 24-week TI responders is similar across key lower-risk MDS subgroups regardless of ringed sideroblast status, prior transfusion burden, IPSS risk category or baseline serum EPO levels. Third, we have presented robust evidence of imetelstat's potential to alter the underlying biology of lower-risk MDS by reducing or eliminating malignant clones.

在EHA 上，我們提出了重要的新亞組分析，顯示TI、24 週TI 反應者的發生率和持久性在關鍵的低風險MDS 亞組中相似，無論環狀鐵粒幼細胞狀態、既往輸血負擔、IPSS 風險類別或基線血清EPO 水平如何。第三，我們提供了強有力的證據，證明 imetelstat 有潛力透過減少或消除惡性克隆來改變低風險 MDS 的潛在生物學特性。

In imetelstat-treated patients, we saw a reduction in mutation burden as measured by variant allele frequency or VAS. Furthermore, new data on cytogenetic responses and reductions in bone marrow RS cells supported imetelstat's mechanism of action. In totality, these data indicate that imetelstat may have disease-modifying potential in patients with lower-risk MDS.

在接受 imetelstat 治療的患者中，透過變異等位基因頻率或 VAS 測量，我們發現突變負擔減少。此外，關於細胞遺傳學反應和骨髓 RS 細胞減少的新數據支持了 imetelstat 的作用機制。總的來說，這些數據表明，imetelstat 對於低風險 MDS 患者可能具有緩解疾病的潛力。

Fourth, data on patient-reported outcomes presented at EHA were also very encouraging. These data describe a sustained meaningful improvement in fatigue for imetelstat-treated patients versus placebo. This specific patient-reported outcome is of particular importance because lower-risk MDS patients experience fatigue that is not fully alleviated by red blood cell transfusions. Additionally, many of the current treatments for lower-risk MDS are associated with an increase in fatigue. Imetelstat is the first treatment we are aware of to show an improvement in patient-reported fatigue in lower-risk MDS patients.

第四，EHA 上公佈的患者報告結果數據也非常令人鼓舞。這些數據描述了與安慰劑相比，伊美司他治療患者的疲勞持續有意義的改善。這種特定的患者報告結果特別重要，因為低風險 MDS 患者會出現疲勞，而紅血球輸注並不能完全緩解疲勞。此外，目前許多低風險骨髓增生異常症候群的治療方法都與疲勞的增加有關。 Imetelstat 是我們所知的第一種能夠改善低風險 MDS 患者報告的疲勞的治療方法。

In IMerge Phase III and consistent with prior clinical experience, Grade 3/4 thrombocytopenias and neutropenias were the most frequently reported adverse events. Unlike several of the treatments in hematologists are momentarium such as HMAs or lenalidomide, which may cause prolonged myelosuppression, the severe cytopenias associated with imetelstat were short-lived, resolving to Grade 2 or lower in less than 4 weeks in most cases and most importantly, only rarely resulted in severe clinical consequences such as bleeding or infection.

在 IMerge III 期中，與先前的臨床經驗一致，3/4 級血小板減少症和嗜中性白血球減少症是最常被通報的不良事件。與血液科醫生的幾種治療方法不同，如HMA 或來那度胺，可能會導致長期骨髓抑制，與伊美司他相關的嚴重血球減少症是短暫的，在大多數情況下，在不到4週的時間內緩解為2 級或更低，最重要的是，很少會導致嚴重的臨床後果，例如出血或感染。

In total, the IMerge clinical data support a profile for imetelstat that if approved, we believe will serve as a very impactful option for the treatment of transfusion-dependent anemia in lower-risk MDS patients.

總的來說，IMerge 臨床數據支持 imetelstat 的概況，如果獲得批准，我們相信將成為治療低風險 MDS 患者輸血依賴性貧血的非常有效的選擇。

Next, I'd like to discuss IMpactMF, our second Phase III trial of imetelstat in patients with JAK inhibitor relapsed/refractory myelofibrosis. Today, treatment of myelofibrosis is dominated by JAK inhibitors or therapies with other mechanisms of action in combination with JAK inhibitors. The currently available therapies have been approved based on their ability to improve symptoms and reduce splenomegaly. Approximately, 75% of patients discontinued JAK inhibitor after 5 years. And once they do so they faced a dismal overall survival of approximately 11 to 16 months.

接下來，我想討論 IMpactMF，這是我們針對 JAK 抑制劑復發/難治性骨髓纖維化患者進行的 imetelstat 的第二項 III 期試驗。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。目前可用的療法已因其改善症狀和減少脾腫大的能力而獲得批准。約 75% 的患者在 5 年後停用 JAK 抑制劑。一旦他們這樣做了，他們就會面臨大約 11 到 16 個月的慘淡總生存期。

We believe that imetelstat could be transformational for these patients. In the IMbark Phase II study and JAK inhibitor relapsed/refractory and mass patients, the overall survival in imetelstat-treated patients was 30 months or nearly double compared to historical controls. Additionally, a comparison of IMbark Phase II data to real-world data from a closely matched cohort of patients confirmed improvement in overall survival and a lower risk of death for imetelstat-treated patients compared with patients treated with best available therapy.

我們相信 imetelstat 可以為這些患者帶來改變。在 IMbark II 期研究和 JAK 抑制劑復發/難治性和腫塊患者中，使用 imetelstat 治療的患者的總存活期為 30 個月，幾乎是歷史對照組的兩倍。此外，將 IMbark II 期數據與密切匹配的患者群組的真實世界數據進行比較，證實與接受最佳可用治療的患者相比，接受 imetelstat 治療的患者總體生存率有所改善，死亡風險更低。

Importantly, in IMbark, there was a strong evidence of the disease-modifying potential of imetelstat in relapsed/refractory MF, with improvements in bone marrow fibrosis and reduction in key MF driver mutations and these reductions correlated to improved survival and other clinical outcomes. These data were the basis for the design and initiation of the IMpactMF Phase III study in JAK inhibitor relapsed/refractory MF patients with overall survival as the primary endpoint.

重要的是，在IMbark 中，有強有力的證據表明imetelstat 在復發/難治性MF 中具有改善疾病的潛力，可以改善骨髓纖維化並減少關鍵的MF 驅動突變，而這些減少與存活率和其他臨床結果的改善相關。這些數據是設計和啟動 IMpactMF III 期研究的基礎，該研究針對 JAK 抑制劑復發/難治性 MF 患者，以總存活期作為主要終點。

The IMpactMF protocol calls for a planned interim analysis in approximately 35% of the planned enrolled patients have died and the final analysis when over 50% of the planned enrolled patients have died. As an OS study, the time line for the interim and final analyses depends not only on enrollment rates but also on death rates. Today, based on achieving over 40% enrollment in IMpactMF and our planning assumptions for enrollment and death rates in the trial, we are updating our guidance for the interim analysis to be projected in the first half of 2025 and for the final analysis to be in the first half of 2026.

IMpactMF 協議要求在大約 35% 的計劃入組患者死亡時進行計劃的中期分析，並在超過 50% 的計劃入組患者死亡時進行最終分析。作為一項 OS 研究，中期和最終分析的時間線不僅取決於入組率，還取決於死亡率。今天，基於IMpactMF 的入組率超過40% 以及我們對試驗中入組率和死亡率的規劃假設，我們正在更新預計於2025 年上半年進行的中期分析的指南，以及將於2025 年上半年進行的最終分析的指南。

Because these analyses are event-driven and it is uncertain whether actual rates for enrollments and events will reflect current planning assumptions, the results may be available at different times than currently projected. As can be expected for a study in an indication for which there are multiple ongoing trials, constraints on clinical site personnel resources due to the COVID-19 pandemic and other competing trials that in MF have led to some challenges in recruitment and enrollment. We are working closely with the MF community and our clinical trial sites on recruitment for the trial and continue to plan to announce when the trial is 50% enrolled.

由於這些分析是由事件驅動的，並且不確定註冊和事件的實際比率是否會反映當前的規劃假設，因此結果可能會在與當前預測不同的時間提供。對於一項正在進行多項試驗的適應症研究來說，可以預見的是，由於COVID-19 大流行和MF 中的其他競爭性試驗對臨床中心人員資源的限制，導致招募和入組方面面臨一些挑戰。我們正在與 MF 社群和我們的臨床試驗中心密切合作，招募試驗人員，並繼續計劃在試驗招募 50% 時宣布。

As Chip mentioned, this is the first and only myelofibrosis trial with overall survival as the primary endpoint. Our MF investigators remain very excited about this study and the potential of a new treatment that could improve survival for these patients who currently have few treatment options and dismal survival rates.

正如 Chip 所提到的，這是第一個也是唯一一個以總存活期為主要終點的骨髓纖維化試驗。我們的 MF 研究人員仍然對這項研究和新療法的潛力感到非常興奮，這種新療法可以提高這些目前治療選擇很少且存活率很低的患者的存活率。

We are also pleased to report that the first patient was dosed this June in the investigator-led Phase II IMpress trial that is evaluating imetelstat in patients with relapsed/refractory acute myeloid leukemia or high-risk MDS. This trial is based on preclinical publications that describe the role of telomeres in AML disease progression and which have reported that inhibiting telomeres in both mouse and human-derived AML models targets and potentially deplete leukemic stem cells, thus impairing leukemic progression. Relapsed/refractory AML and higher-risk MDS are high unmet need areas and we look forward to understanding more about the potential efficacy of imetelstat in this patient population.

我們也很高興地報告，今年6 月，在研究者主導的II 期IMpress 試驗中，第一位患者接受了給藥，該試驗正在評估imetelstat 對復發/難治性急性髓性白血病或高風險MDS 患者的療效。該試驗基於臨床前出版物，這些出版物描述了端粒在AML 疾病進展中的作用，並報告在小鼠和人源性AML 模型中抑制端粒可以靶向並可能耗盡白血病幹細胞，從而損害白血病進展。復發/難治性 AML 和高風險 MDS 是未滿足的需求領域，我們期待更多地了解 imetelstat 在該患者群體中的潛在療效。

With that, let me turn the call over to Anil to provide a commercial update. Anil?

接下來，讓我將電話轉給阿尼爾，以提供商業更新。阿尼爾？

Thank you, Faye, and good afternoon, everyone. We are very pleased with the status of our commercial readiness activities and are on track to achieve launch readiness by early 2024. Faye has already described several significant efforts that support potential imetelstat launch, including important regulatory progress as well as unprecedented IMerge data presented at medical meetings, which deeply support imetelstat's value proposition messaging.

謝謝你，Faye，大家下午好。我們對商業準備活動的狀態感到非常滿意，並預計在2024 年初實現發布準備。數據。

In particular, the PRO data reporting improvement in fatigue with imetelstat is an important differentiator and will be a critical element for PAR interactors. This quarter, we also advanced critical work by obtaining significant insights from our market research efforts based on the latest lower-risk MDS data presented at ASCO and EHA by Geron and competitors. For a full review of this market research, we refer you to the Investor Event webcast that Faye mentioned earlier.

特別是，PRO 數據報告的 imetelstat 疲勞改善是一個重要的差異化因素，並將成為 PAR 互動器的關鍵要素。本季度，我們也根據 Geron 和競爭對手在 ASCO 和 EHA 上提供的最新低風險 MDS 數據，從市場研究工作中獲得了重要見解，從而推進了關鍵工作。要完整回顧本次市場研究，我們建議您參閱 Faye 之前提到的投資者活動網路廣播。

For purposes of today's call, I will highlight key takeaways from that market research presentation. First, in alignment with informal feedback on the grounds at ASCO and EHA, our latest market research from practicing academic and community hematologists across U.S. and key European markets confirmed that our IMerge Phase III data has been received favorably, particularly the compelling TI rates across subgroups, reduction in transfusion burden, hemoglobin rises, meaningful durability of response, balanced with the predictable adverse event profile with manageable cytopenias. Second, continued hematologist feedback supports the imetelstat opportunity across ESA, relapsed/refractory Rh-negative and Rh-positive subtypes as well as high transfusion burden patients.

在今天的電話會議中，我將重點放在該市場研究演講的主要內容。首先，根據ASCO 和EHA 的非正式反饋，我們對美國和歐洲主要市場的執業學術和社區血液學家進行的最新市場研究證實，我們的IMerge III 期數據受到了好評，特別是各個亞組令人信服的TI 率，輸血負擔減少，血紅蛋白升高，有效的反應持久性，與可預測的不良事件和可控制的血球減少相平衡。其次，持續的血液學家回饋支持伊美司他在 ESA、復發/難治性 Rh 陰性和 Rh 陽性亞型以及高輸血負擔患者的機會。

Third, these hematologists indicated that imetelstat is likely to become a new standard of care in post ESA experience and imetelstat's experienced frontline patients or second-line lower-risk MDS patients as well as an important new option for frontline ESA-ineligible patients whose serum equal level is greater than 500. All of these insights are instrumental to our understanding of imetelstat's potential place in the market and our engagement strategy with physicians.

第三，這些血液學家表示，imetelstat 很可能成為 ESA 後經驗的新護理標準，並且 imetelstat 的經驗豐富的一線患者或二線低風險 MDS 患者以及血清等於一線 ESA 不合格患者的重要新選擇水平大於500 。

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

這樣，我會將電話轉給奧莉維亞，以了解完整的財務最新情況。奧莉薇亞？

Thanks, Anil, and thanks to everyone on the call for joining us today. Please refer to the press release we issued this afternoon, which is available on our website for detailed financial results. As expected, operating expenses were higher for the 3 and 6 months ended June 30, 2023, compared to the prior period.

謝謝阿尼爾，也感謝今天參加我們電話會議的所有人。請參閱我們今天下午發布的新聞稿，該新聞稿可在我們的網站上查看詳細的財務業績。正如預期的那樣，截至 2023 年 6 月 30 日的 3 個月和 6 個月的營運費用高於上一期間。

The increase in R&D expenses for the 3- and 6-month periods of 2023 compared to the same period in 2022 primarily reflects higher clinical trial costs for increased activity for both Phase III trials and the Phase I trial in frontline MF, increased personnel-related costs for additional head count, higher consulting costs to support regulatory submissions and greater imetelstat manufacturing costs in preparation for potential commercialization in the first half of 2024 in lower-risk MDS. The increase in general and administrative expenses for the 3 and 6 months ended June 30, 2023, compared to the same period in 2022 primarily reflects higher personnel-related expenses for additional head count and increased costs for new commercial preparatory activities.

與 2022 年同期相比，2023 年 3 個月和 6 個月的研發費用增加，主要反映了一線 MF 的 III 期試驗和 I 期試驗活動增加、人員相關的增加導致臨床試驗成本增加。的成本、支援監管提交的更高諮詢成本以及更高的imetelstat 製造成本，為2024 年上半年低風險MDS 的潛在商業化做準備。與 2022 年同期相比，截至 2023 年 6 月 30 日的 3 個月和 6 個月的一般和管理費用增加，主要反映了人員增加的人事相關費用增加以及新商業準備活動成本的增加。

We continue to expect non-GAAP total operating expenses of up to $210 million for the full year of 2023. This financial guidance may be revised in the future upon notification from the FDA of the potential approval timing for imetelstat in low-risk MDS.

我們仍預計 2023 年全年的非 GAAP 總營運費用將高達 2.1 億美元。

Turning to our financial resources. As of June 30, 2023, we had approximately $400.2 million in cash and marketable securities. This balance includes approximately $17.8 million in proceeds from warrant exercises that we received in the second quarter of 2023. In the first half of 2023, in total, we have received approximately $77.6 million in warrant proceeds, which leaves approximately $32 million in potential future warrant proceeds remaining to be exercised.

轉向我們的財政資源。截至 2023 年 6 月 30 日，我們擁有約 4.002 億美元的現金和有價證券。該餘額包括我們在2023 年第二季收到的約1,780 萬美元的認股權證收益。美元的未來潛在認股權證所得款項尚待行使。

Based on our current operating plans and our expectations regarding the timing of the submission and potential acceptance and approval of our NDA by the FDA for imetelstat in lower-risk MDS and the subsequent potential U.S. commercial launch in the first half of 2024 as well as the revised guidance on timing of the interim and final analyses for IMpactMF, we believe that our existing financial resources and estimated revenue will be sufficient to fund our projected operating requirements through the end of the third quarter of 2025. If projected exercise proceeds of approximately $32 million from remaining outstanding warrants are added to our current financial resources and estimated revenue, then we believe such aggregated financial resources will be sufficient to fund our projected operating requirements through the end of 2025.

根據我們目前的營運計劃以及我們對 FDA 提交用於低風險 MDS 的 imetelstat 的 NDA 的提交時間和潛在接受和批准的預期，以及隨後可能於 2024 年上半年在美國商業上市的預期，以及關於IMpactMF 中期和最終分析時間的修訂指南，我們相信我們現有的財務資源和估計收入將足以滿足我們到2025 年第三季末的預計營運需求。股權證添加到我們目前的財務資源和估計收入中，那麼我們相信這些匯總的財務資源將足以滿足我們到2025 年底的預期營運需求。

With that, I will now hand the call back to Chip for closing remarks. Chip?

現在，我將把電話轉回給奇普，讓其結束語。晶片?

Thanks, Olivia. I'd like to close by reiterating what an exciting time this is for Geron, for imetelstat and for the MDS community. Based on our unprecedented Phase III data in lower-risk MDS and an outpouring of enthusiasm from the medical community, we believe that imetelstat could transform the standard of care in lower-risk MDS.

謝謝，奧莉維亞。最後，我想重申，對於 Geron、imetelstat 和 MDS 社群來說，這是多麼令人興奮的時刻。基於我們在低風險 MDS 方面前所未有的 III 期數據以及醫學界的熱情，我們相信 imetelstat 可以改變低風險 MDS 的護理標準。

We're also very proud to be pioneering the first study in myelofibrosis with overall survival as the primary endpoint. We believe that a potentially disease-modifying treatment that improves survival could be transformational for these patients who have failed JAK inhibitors and have limited other options. As a result, we'll stay the course of this Phase III trial, especially given its immense potential for value creation for patients and shareholders alike.

我們也非常自豪能夠率先開展第一項以總存活期為主要終點的骨髓纖維化研究。我們相信，對於那些 JAK 抑制劑失敗且其他選擇有限的患者來說，一種可以提高存活率的潛在疾病緩解治療可能會帶來改變。因此，我們將繼續進行第三階段試驗，特別是考慮到它為患者和股東創造價值的巨大潛力。

Finally, we look forward to the expected momentum in the months to come as we continue to execute on our commercial readiness plan and ultimately to a potential U.S. launch of imetelstat in the first half of 2024.

最後，我們期待未來幾個月的預期勢頭，因為我們將繼續執行我們的商業準備計劃，並最終預計在 2024 年上半年在美國推出 imetelstat。

So operator, with that, let's open the call to Q&A.

接線員，現在讓我們開始問答環節。

(Operator Instructions) And we do have our first person in the queue. Kalpit Patel, please go ahead.

（操作員說明）我們確實有第一個人在隊列中。卡爾皮特·帕特爾，請繼續。

Yes. Congrats on the NDA submission. So maybe starting with one question for Anil. For lower-risk MDS assuming that we get approval here in the near future, what early launch metrics do you believe will be important to showcase and highlight the initial stages of launch?

是的。恭喜您提交 NDA。那也許可以先問阿尼爾一個問題。對於風險較低的 MDS，假設我們在不久的將來獲得批准，您認為哪些早期啟動指標對於展示和強調啟動的初始階段非常重要？

Thank you, Kalpit. I think for us, it's really important that we have full coverage across reimbursement policies for both academic and community centers. That's really critical for a new drug at the time of launch. And it's our expectation that we are going to probably inform the market and make sure that the policy, the reimbursement blocks, things that are really critical for the new drugs get addressed well.

謝謝你，卡爾皮特。我認為對我們來說，全面涵蓋學術和社區中心的報銷政策非常重要。這對於新藥上市時確實至關重要。我們期望我們能夠向市場通報情況，並確保政策、報銷區塊以及對新藥真正至關重要的事情得到很好的解決。

We are also going to measure uptake across both academic and community channels for physicians and the type of patients that are on imetelstat. And since these will be early days, we will obviously continue to monitor for durability of response and questions that may come up around reimbursement and ensuring broadest to possible access in the very early days of launch. And from a supply chain perspective, making sure that the drug through specialty distributors is going to patients properly.

我們還將衡量醫生在學術和社區管道上的使用情況以及使用 imetelstat 的患者類型。由於現在還處於早期階段，我們顯然將繼續監控回應的持久性和可能出現的有關報銷的問題，並確保在發布的最初幾天獲得盡可能廣泛的訪問。從供應鏈的角度來看，確保藥物透過專業經銷商正確到達患者手中。

We also will have our patient hub activated. And so this is to ensure seamless distribution of the drug and wider access to the patient. So those would be the first few things that we'll focus on.

我們還將啟動我們的患者中心。這是為了確保藥物的無縫分配和更廣泛地接觸到患者。因此，這些將是我們首先關注的幾件事。

Okay. Perfect. And then for the IMpactMF study, just curious, as the enrollment rate be impacted because of any potential competition from other clinical studies and can you maybe add additional clinical trial sites to streamline the enrollment there or is that not an option?

好的。完美的。然後對於 IMpactMF 研究，只是好奇，因為來自其他臨床研究的任何潛在競爭會影響入組率，您是否可以添加額外的臨床試驗地點來簡化那裡的入組，或者這不是一個選擇？

Faye, do you want to take that?

菲，你想要那個嗎？

Sure. Thanks for the question, Kalpit. Despite the fact that these patients have a high unmet need for alternative JAK inhibitor therapies, there are indeed, as you mentioned, a number of other ongoing clinical trials in this space. And it's not so much the competition for patients necessarily for these trials. It's more the resources and the staffing given that myelofibrosis is an orphan and rare disease, there's limited like research staff that can be devoted to studies. So I think that is part of the -- so that is part of the delay in enrollment. Regardless, we continue to believe in the study and the likelihood of a positive readout and the potential for the study to change the course of MF treatment.

當然。謝謝你的提問，卡爾皮特。儘管這些患者對替代 JAK 抑制劑療法的需求尚未得到滿足，但正如您所提到的，該領域確實還有許多其他正在進行的臨床試驗。這些試驗並不一定是對患者的競爭。更重要的是資源和人員配置，因為骨髓纖維化是一種罕見的罕見疾病，能夠投入研究的研究人員是有限的。所以我認為這是入學延遲的一部分。無論如何，我們仍然相信這項研究、積極讀數的可能性以及該研究改變 MF 治療過程的潛力。

Okay. Got it. And one last question on the competitive landscape for myelofibrosis here. We're anticipating data for the combo from MorphoSys in the second half in frontline myelofibrosis. Assuming that the study hits its endpoint, does that in any sense impact your development strategy in myelofibrosis and post-drug stations?

好的。知道了。最後一個問題是關於骨髓纖維化的競爭格局。我們預計下半年 MorphoSys 組合在一線骨髓纖維化的數據。假設研究達到終點，這是否會在任何意義上影響您在骨髓纖維化和藥物後站的開發策略？

Sure. There's -- it doesn't necessarily -- it doesn't change the current status of our Phase III study, which is looking at patients who have failed JAK inhibitor and are not eligible for JAK inhibitor. So patients, whether they were treated on a clinical trial or as part of standard of care in the community will still be eligible for the IMpactMF trial. And I think regardless of the readout, our former focus there is still an unmet need for patients after they fail JAK inhibitor.

當然。這不一定——它不會改變我們 III 期研究的當前狀態，該研究正在研究 JAK 抑製劑失敗且不符合 JAK 抑製劑資格的患者。因此，患者無論是接受臨床試驗治療還是社區標準護理的一部分，仍然有資格參加 IMpactMF 試驗。我認為，無論結果如何，我們先前的重點是，在 JAK 抑制劑失效後，患者的需求仍然未被滿足。

Our next question comes from the line of Robert Driscoll.

我們的下一個問題來自羅伯特·德里斯科爾。

This is [Sam] on for Robert today. I'm just wondering how you might be able to address any doctor concerns or apprehension around the temporary cytopenias associated with imetelstat treatment ahead of commercialization or if there are any other potential gating factors to broad uptake that you're working to address?

這是[山姆]今天為羅伯特所做的。我只是想知道，在商業化之前，您如何能夠解決醫生對與 imetelstat 治療相關的暫時性血球減少症的擔憂或擔憂，或者您正在努力解決是否存在其他潛在的廣泛採用的限制因素？

Why don't you go ahead first, Faye?

菲，為什麼不先走呢？

I can...

我可以...

Sorry. Go ahead, Anil.

對不起。繼續吧，阿尼爾。

Okay. So let me start first, Robert, and I'll ask Faye to jump in as well. So we have shared the full safety profile of our drug with the IMerge study results with a broad set of physicians, both community, academic across both the U.S. and key European markets. The feedback we have received multiple times over the last few years has been that the focus from physicians remains on the timing of cytopenias, the resolution data and more specifically on the clinical consequences, especially bleeding, infections and hospitalizations. And they have also compared the imetelstat arm to the placebo arm in the trial.

好的。那麼，羅伯特，我先開始，我也會請費耶加入。因此，我們與美國和歐洲主要市場的廣大醫生（包括社區醫生、學術界醫生）分享了我們藥物的完整安全性和 IMerge 研究結果。過去幾年我們多次收到的回饋是，醫生的重點仍然是血球減少的時間、解決數據，更具體地說是臨床後果，特別是出血、感染和住院。他們還在試驗中將 imetelstat 組與安慰劑組進行了比較。

Overall, we see very similar conclusions for both academic and community doctors and we expect that the AE profile as per them is not a barrier at the time of launch. All sites, very extensive experiences with managing new toxicities in this setting, especially given long-term familiarity with HMAs and them. And they also state that they'll obviously manage their first patients as they build clinical experience with the drug more closely.

總的來說，我們看到學術界和社區醫生得出的結論非常相似，我們預計他們的 AE 概況在發佈時不會成為障礙。所有地點在管理這種環境下的新毒性方面都有非常豐富的經驗，特別是考慮到對 HMA 及其本身的長期熟悉。他們還表示，隨著他們更密切地累積該藥物的臨床經驗，他們顯然將管理第一批患者。

So our expectation is, given the very high efficacy results, the clear mechanistic rationale for why these cytopenias occur, the fact they're predictable and the fact there are few clinical consequences, this should be really good. And it would be our medical affairs teams, our entire teams and we'll continue to focus on education and the linkage to the mechanism of action so they have a clear understanding of what to expect for imetelstat patients and ensure success. Faye, if you would like to add anything clinically from your side?

因此，我們的期望是，鑑於非常高的療效結果、這些血球減少症發生的明確機制原理、它們是可預測的事實以及幾乎沒有臨床後果的事實，這應該是非常好的。這將是我們的醫療事務團隊，我們的整個團隊，我們將繼續專注於教育和與行動機制的聯繫，以便他們清楚地了解 imetelstat 患者的期望並確保成功。 Faye，您想補充一些臨床的內容嗎？

Sure. I completely agree and echo with what Anil said and the feedback that we hear really is from hematologists. They are comfortable at managing cytopenias and understanding them and knowing what measures to take in order to support their patients once we explain the timing, the reversibility and most importantly, the lack of prolonged cytopenias and lack of severe infections or severe bleeding, there really -- once there's an understanding for that, it helps to allay any possible concerns, but mostly in the hands of hematologists, they feel quite comfortable managing these cytopenias. And also in the upcoming months, as Anil mentioned, we'll have training from our medical affairs team and also more insight into cytopenias in further like presentations or publications.

當然。我完全同意並同意阿尼爾的說法，我們聽到的回饋確實來自血液學家。一旦我們解釋了發生的時間、可逆性，最重要的是，沒有長期的血球減少症，也沒有嚴重的感染或嚴重的出血，他們就能夠輕鬆地處理血球減少症並了解它們，並知道應該採取哪些措施來支持他們的患者，真的- - 一旦對此有了了解，就有助於減輕任何可能的擔憂，但主要是在血液學家手中，他們對處理這些血球減少症感到非常自在。正如阿尼爾所提到的，在接下來的幾個月裡，我們將接受醫療事務團隊的培訓，並透過演示或出版物等形式進一步深入了解血球減少症。

That's helpful. And then just one last one here. Just kind of wondering if there are any key differences between the value proposition for imetelstat in the U.S. versus the EU, just based on the current treatment paradigms for each region?

這很有幫助。然後這裡只有最後一張。只是想知道僅基於每個地區目前的治療範例，美國與歐盟的 imetelstat 價值主張是否存在任何關鍵差異？

Anil?

阿尼爾？

I think let me take that, yes, sir. So let me take that question, Robert, with EU first. As you can imagine, the most important thing in Europe is to establish broad-based reimbursement, each of the countries is very different. And what's really encouraging about imetelstat and low-risk MDS is our efficacy datasets are all showing the data that payers have repeatedly asked for. This includes PRO data. It includes 24-week PR data, which they have insisted that they would really like to see.

我想讓我接受，是的，先生。羅伯特，讓我先向歐盟提出這個問題。你可以想像，歐洲最重要的是建立廣泛的報銷，每個國家都有很大的不同。 imetelstat 和低風險 MDS 真正令人鼓舞的是我們的療效數據集都顯示了付款人反覆要求的數據。這包括 PRO 數據。其中包括 24 週的公關數據，他們堅稱他們確實希望看到這些數據。

And that is very positive news for us because the durability of PR and the CRO value proposition is very strong. So our goal there is to establish [FISA] in all the key markets in sequence. And I think we'll be favorably received within Europe. In U.S., again, the goal here is we have a concentrated set of our physician universe and our aim here is to make sure that imetelstat is launched really well and these physicians have first (inaudible) success.

這對我們來說是非常正面的消息，因為 PR 和 CRO 價值主張的持久性非常強。因此，我們的目標是依序在所有主要市場建立 [FISA]。我認為我們會在歐洲受到好評。同樣，在美國，我們的目標是我們擁有一批集中的醫生群體，我們的目標是確保 imetelstat 能夠很好地推出，並且這些醫生取得第一次（聽不清楚）成功。

In terms of commercial value, obviously, as you know, it's pricing-dependent. So the U.S. market is commercially more dollar value higher than the European market. But the adoption and the need for imetelstat comes out pretty equally across both the U.S. and Europe.

就商業價值而言，如您所知，顯然它取決於定價。所以美國市場的商業價值比歐洲市場更高。但在美國和歐洲，imetelstat 的採用率和需求量幾乎相同。

Our next question comes from the line of Corinne Jenkins.

我們的下一個問題來自 Corinne Jenkins。

Maybe a couple from me. On the EAP, what can you share regarding kind of the initial demand you're seeing for that program and where are the pockets of that demand coming from and how are you managing to hear that program ahead of the launch?

也許是我的一對。在 EAP 上，您能分享一下您對該計劃的最初需求嗎？

Sure. I'll take that. This is Faye. So the expanded access protocol was recently opened and approved and really is a bridge for -- or a mechanism for patients to receive imetelstat prior to approval and commercialization. The way that the EAP protocol is structured is that the patient care providers, the physicians place a request on an individual patient basis for an enrollment into the protocol and then it's very similar to any other type of clinical trial protocol. So it's still early on in our opening of it and we don't yet have a sense of what we -- the kinetics of the enrollment.

當然。我會接受的。這是菲伊。因此，擴展訪問協議最近開放並獲得批准，實際上是患者在批准和商業化之前接受 imetelstat 的橋樑或機制。 EAP 協議的建構方式是病患照護提供者、醫師根據個別病患提出加入協議的請求，然後它與任何其他類型的臨床試驗協議非常相似。因此，我們還處於開放的早期階段，我們還不清楚招生的動態。

Okay. Understood. And then maybe separately, I think I saw in the press release, you expect the growth in terms of employees to be up to about 160 by the end of the year. At that point, how much additional hiring will you need to do to be prepared for the launch?

好的。明白了。然後，也許單獨來看，我想我在新聞稿中看到，您預計到今年年底員工人數將增長到 160 人左右。到那時，您需要額外招募多少人才能為發布做好準備？

Corinne, just a (inaudible) question. So that total does not include the sales force that is going to need to be hired for launch because that is -- the timing of that hiring is going to be dependent on the PDUFA date. And then I'll hand the microphone over to Anil to talk about the size of the sales force and what's going to be necessary.

Corinne，只是一個（聽不清楚）問題。因此，這個總數不包括為發布而需要雇用的銷售人員，因為招募的時間將取決於 PDUFA 日期。然後我會將麥克風交給阿尼爾，討論銷售團隊的規模以及需要什麼。

Yes. So as we have previously guided, Corinne, on that answer, our sales force field expansion will be very PDUFA-aligned and our expectation is a national competitive coverage. And as we previously said, we expect our commercial organization to be somewhere in the 100 to 120 full-time people including sales and the commercial team supporting us across medical affairs as well as the commercial side of it.

是的。 Corinne，正如我們之前就這個答案所指導的那樣，我們的銷售隊伍領域擴張將非常符合 PDUFA，我們的期望是全國性的競爭覆蓋。正如我們之前所說，我們預計我們的商業組織將擁有 100 到 120 名全職員工，包括銷售和商業團隊，為我們的醫療事務及其商業方面提供支援。

Our next question comes from the line of Gil Blum.

我們的下一個問題來自吉爾·布魯姆（Gil Blum）。

Maybe a simple one first. So we expect news on some FDA feedback soon in August. Will we know also about an advisory committee at that point or could that take a little longer?

也許首先是一個簡單的。因此，我們預計 8 月將很快收到有關 FDA 反饋的消息。屆時我們是否還會知道諮詢委員會的存在，或是否需要更長的時間？

I'll take that one, Gil. Ordinarily, we wouldn't know about advisory committee either plus or minus at that time. The agency is usually very focused on an acceptance of the NDA for review, in their lingo, the filing of the NDA. That's the one thing that we can count on. We would next expect to hear possibly by the end of the month of August, something further about the actual PDUFA date, assuming that it's accepted, which would give us an indication of whether it was a priority or a standard review.

我要那個，吉爾。通常情況下，我們當時不知道諮詢委員會的正負。該機構通常非常注重接受 NDA 進行審查，用他們的行話來說，就是 NDA 的備案。這是我們可以信賴的一件事。接下來，我們預計可能會在 8 月底聽到有關實際 PDUFA 日期的進一步消息（假設它被接受），這將使我們知道它是優先審查還是標準審查。

If and when there would be an advisory committee meeting in ODAC, quite uncertain when that would be announced or requested or posted. It can come quite late in the review cycle. It can come a little bit earlier, but there's no specific timing for that. And I don't think we would have any feel for that right now.

ODAC 是否以及何時召開諮詢委員會會議，尚不確定何時宣布、要求或發布。它可能在審查週期中很晚才出現。它可能會提前一點，但沒有具體的時間。我認為我們現在不會對此有任何感覺。

Maybe a bit of a broader question on -- a clinical one. Is there any understanding regarding the non-responders in lower-risk MDS? Is this just because the primary disease is too far longer? What are your insights on patients who seem to not respond?

也許是一個更廣泛的問題——臨床問題。對於低風險 MDS 中的無反應者是否有任何了解？難道只是因為原發病時間太長了？您對似乎沒有反應的患者有什麼看法？

That's a great question, Gil. So you're asking about the patients who probably don't achieve TI. A lot of those patients, though they may not achieve 100% transfusion independence, they may have reductions in transfusion burden. They may have increases in hemoglobin, improvement in symptoms or other quite possibly like intangible benefits or benefits that were not routinely assessed on the study. So we continue to look into that and we continue to look into if there are any predictors of patients who will achieve TI in terms of mutation or pathology or anything like that and we have not yet seen anything notable distinguishing patients to achieve TI from those who don't.

這是一個很好的問題，吉爾。所以您詢問的是可能未達到 TI 的患者。其中許多患者雖然可能無法達到 100% 的輸血獨立，但輸血負擔可能會減輕。他們可能會增加血紅蛋白、改善症狀或其他很可能類似的無形益處或研究中未常規評估的益處。因此，我們將繼續研究這一點，並繼續研究是否存在任何在突變或病理學或類似方面可以實現TI 的患者的預測因素，而且我們尚未看到任何顯著的特徵將實現TI 的患者與那些未達到TI 的患者區分開來。

Our next question comes from the line of [Tuli].

我們的下一個問題來自[Tuli]的台詞。

Hi. This is [Tuli] on for Stephen Willey at Stifel. I just have one quick question regarding IMpactMF. So with the 40%, if I remember correctly, with 40% of patients enrolled in this study now, can you guys maybe talk a little bit about how -- so basically the -- whether the early event rate that you have observed to-date is in line with your expectation? And also can you also give us a little bit of color on maybe the efforts or anything that you're doing to expedite enrollment in IMpactMF?

你好。這是 Stifel 的 Stephen Willey 的 [Tuli]。我只是有一個關於 IMpactMF 的簡單問題。因此，如果我沒記錯的話，現在有 40% 的患者參加了這項研究，你們能否談談——基本上是——你們觀察到的早期事件發生率是如何——日期符合你們的預期嗎？另外，您能否向我們介紹一下您為加快 IMpactMF 註冊所做的努力或所做的任何事情？

Sure. This is Faye. I'll take that question. Regarding the event rate, given that this is a blinded study, although the patients know which arm they're randomized to, we are blinded to the data and to what patients are taking when we look at the analysis as a whole. So we cannot comment on the event rate until basically either the interim or the final analysis when the study is unblinded. But just to say also that the 40% enrollment to contrast, that would say 35% of the enrolled patients having died is when the interim is triggered.

當然。這是菲伊。我來回答這個問題。關於事件發生率，鑑於這是一項盲法研究，儘管患者知道他們被隨機分配到哪一組，但當我們從整體上看待分析時，我們對數據和患者正在服用的藥物並不了解。因此，在非盲研究的中期或最終分析之前，我們無法對事件發生率發表評論。但還要說的是，與 40% 的入組率相比，這意味著 35% 的入組患者在暫時觸發時死亡。

So -- and then to move to your second question about efforts to expedite or to boost enrollment. We have had ongoing efforts since end of last year, early this year, which included site visits and investigator engagements and additional resourcing to encourage enrollment and boost enrollment. We continue to receive enthusiastic feedback from MF investigators for the study and for enrolling patients in the study and we hope that the efforts that we've put in to-date will continue to bear fruit and we'll see that, that helps and maintains our enrollment.

那麼，然後轉向關於加快或提高入學率的努力的第二個問題。自從去年底、今年年初以來，我們一直在不斷努力，其中包括實地考察和調查員參與以及額外資源以鼓勵入學和提高入學率。我們繼續收到 MF 研究人員對這項研究和招募患者的熱情反饋，我們希望我們迄今為止所付出的努力將繼續取得成果，我們會看到這一點，這有助於並維持我們的招生。

(Operator Instructions) Our next question comes from Joel Beatty.

（操作員說明）我們的下一個問題來自 Joel Beatty。

The first one is a follow-up on the previous question on IMpactMF. So with that guidance now being for interim readout in first half of 2025, is that timing driven solely by the enrollment rate or does it also take into consideration the event rate on a blended basis?

第一個是 IMpactMF 上一個問題的後續。那麼，現在該指導方針是針對 2025 年上半年的臨時讀數，該時間安排是僅由入學率決定還是還綜合考慮了事件發生率？

Thanks for the question. So the -- it takes into account the current enrollment rate and what we've seen in enrollment now that the study has been open for some time, we have a better or more of a sense now for the pace of enrollment. But the event rate is based on the initial one from the assumption built into the study. And at the time, we haven't recalibrated the event rate.

謝謝你的提問。因此，它考慮到了目前的入學率以及我們在入學中所看到的情況，因為研究已經開放了一段時間，我們現在對入學速度有了更好或更多的了解。但事件發生率是基於研究中假設的最初事件發生率。當時，我們還沒有重新校準事件發生率。

And then on MDS, now that ASCO has passed, can you discuss where you see is the opportunity to capture market share in RS-negative patients, which is, as I understand it, the majority of the market and also where luspatercept have showed a negative trend on the primary endpoint?

然後，關於MDS，現在ASCO 已經通過了，您能討論一下您認為在RS 陰性患者中奪取市場份額的機會嗎？ 。

Anil?

阿尼爾？

Sure, I can -- yes. I can take that question there. So I think the data is very clear. What we are seeing in terms of sequencing post-ASCO and EHA update on all the data that came out at lower-risk MDS, in RS-negative patients, the strong preference for physician remains imetelstat, especially in patients who are previously ESA-treated. And that is pretty overwhelming both from U.S. perspective as well as from a European perspective.

當然，我可以——是的。我可以在那裡提出這個問題。所以我覺得這個數據是非常清楚的。我們在 ASCO 後定序和 EHA 更新的所有低風險 MDS 數據中看到，在 RS 陰性患者中，醫生仍然強烈偏好 imetelstat，特別是在先前接受過 ESA 治療的患者中。無論從美國的角度還是從歐洲的角度來看，這都是相當壓倒性的。

So that's very consistent. And I think that is in line with what we know previously from the PACE study and also, obviously, from the COMMANDS trial in the frontline setting. So we feel that imetelstat is likely to become the standard of care in RS-negative patients, especially the ESA-treated patient population, which will be the vast majority and that is irrespective of transfusion burden. So that is good for patients and there's a validation for the data that came out from (inaudible).

所以這是非常一致的。我認為這與我們之前從 PACE 研究以及前線環境中的 COMMANDS 試驗中了解到的情況一致。因此，我們認為，imetelstat 很可能成為 RS 陰性患者的照護標準，尤其是接受 ESA 治療的患者群體，這將佔絕大多數，並且與輸血負擔無關。因此，這對患者有好處，並且對來自（聽不清楚）的數據進行了驗證。

Terrific. And one last question is on operating expenses. That looked up a bit from about $40 million in Q1 to about $52 million now in Q2. Can you help put that increase into context and give a sense of what that trajectory in expenses might look like over the next quarter or 2?

了不起。最後一個問題是關於營運費用。這一數字從第一季的約 4,000 萬美元上升到第二季的約 5,200 萬美元。您能否幫助我們了解這一成長情況，並了解未來一兩個季度的支出軌跡可能會是什麼樣子？

Yes, Joel. It's Olivia. Thanks for the question. So as I mentioned and we're still maintaining our overall annual guidance of up to $210 million of non-GAAP expense. And as I think I've said on previous calls that I did anticipate that getting towards the second half of the year, the ramp in expenses, especially not only is the more intensified commercial prep efforts, but also as we are manufacturing commercial grade inventory getting ready for launch as well.

是的，喬爾。這是奧莉維亞。謝謝你的提問。正如我所提到的，我們仍然維持高達 2.1 億美元的非 GAAP 支出的年度整體指引。正如我在之前的電話會議中所說的那樣，我確實預計到今年下半年，費用會增加，特別是不僅是更加強的商業準備工作，而且是因為我們正在製造商業級庫存也在為發射做準備。

And so that's where you're seeing the increase happening here in the second quarter in comparison to the first quarter is that there were increased expenses related to manufacturing costs as well as, I would say, increased costs for consulting expenses as we have submitted all of the regulatory filings related to the NDA and then now in the heart of getting everything ready for the MAA filing here in the fourth quarter of 2023.

因此，與第一季相比，您看到第二季度發生的成長是與製造成本相關的費用增加，以及諮詢費用的增加，因為我們已經提交了所有我們正在處理與NDA 相關的監管備案，現在正為2023 年第四季的MAA 備案做好一切準備。

And there are no further questions. So at this time, I would like to turn it back over to Aron Feingold.

沒有其他問題了。所以這個時候，我想把它轉回給 Aron Feingold。

Thank you so much for joining us today. We appreciate you taking the time to listen and participate and look forward to keeping you updated on our progress.

非常感謝您今天加入我們。我們感謝您花時間傾聽和參與，並期待向您通報我們的最新進展。

That concludes today's call. You may disconnect.

今天的電話會議到此結束。您可以斷開連線。