Geron Corp (GERN) 2024 Q1 法說會逐字稿

Thank you for standing by. My name is Jill, and I will be your conference operator today. At this time, I would like to welcome everyone to the Geron Q1 2024 conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one. Again, I would now like to turn the conference over to Aron Feingold, you may begin.

謝謝你的支持。我叫吉爾，今天我將擔任你們的會議操作員。此時此刻，我歡迎大家參加 Geron 2024 年第一季電話會議。所有線路均已靜音，以防止任何背景噪音。演講者發言後，將進行問答環節。如果您想在此期間提出問題，只需按電話鍵盤上的星號，然後再按數字 1 即可。如果您想撤回問題，請按星號一。再說一次，我現在想把會議交給 Aron Feingold，您可以開始了。

Good morning, everyone. Welcome to the Geron Corporation First Quarter 2024 earnings conference call and Aron Feingold Geron's, Vice President of Investor Relations and Corporate Communications.

大家，早安。歡迎參加 Geron Corporation 2024 年第一季財報電話會議以及投資人關係與企業傳播副總裁 Aron Feingold Geron 的電話會議。

I'm joined today by several members of Darren's management team, Dr. John Scarlett, Chairman and Chief Executive Officer, Neil Cooper, Executive Vice President of Corporate Strategy and Chief Commercial Officer, Dr. Faiz seller, Executive Vice President and Chief Medical Officer, Michelle Robertson, Executive Vice President and Chief Financial Officer, and Dr. Andrew Crestline, Executive Vice President and Chief Operating Officer.

今天加入我的還有達倫管理團隊的幾位成員：董事長兼執行長約翰·斯嘉麗博士、企業策略執行副總裁兼首席商務官尼爾·庫珀、執行副總裁兼首席醫療官法伊茲·塞勒博士、執行副總裁兼首席財務官米歇爾·羅伯遜 (Michelle Robertson) 和執行副總裁兼首席營運官安德魯·克雷斯特林 (Andrew Crestline) 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. Therefore, I refer you to the discussion under the heading Risk Factors.

在我們開始之前，請注意，在本次演示和問答環節中，我們將對未來事件、績效計劃、期望和其他預測做出前瞻性陳述，包括與治療潛力和潛力相關的前瞻性陳述imetelstat 的監管批准、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、實際事件或結果的陳述可能存在重大差異。因此，我建議您參閱“風險因素”標題下的討論。

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.

Geron 在向美國證券交易委員會提交的最新定期報告中指出了可能導致實際結果與前瞻性陳述中包含的結果有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. Jeff?

這樣，我會將電話轉給 Chip。傑夫？

Thank you, and good morning, everyone. Thanks for joining us. We're poised for a successful U.S. launch of imetelstat for the treatment of transfusion dependent anemia in patients with lower-risk MDS. If approved, we're deeply excited for the opportunity to bring patients what we believe is an important and differentiated medicine with our PDUFA date on June 16th. We continue to work closely with the FDA as they complete the review of our new drug application as part of the NDA review process on March 14th, the FDA's Oncology Drug Advisory Committee or Kodak, voted 12 to two in favor of the clinical benefit risk profile with Imetelstat for its intended indication in lower-risk MDS. The resounding support for imetelstat reflected in the order backlog was also echoed in comments from the lower-risk MDS community. During the public forum, hematologists and patients alike spoke about the burden of transfusion dependent anemia in this disease and the need for new treatments, particularly for patients with difficult-to-treat subtypes, such as high transfusion burden and RS negative patients. Imetelstat is uniquely positioned to address these underserved transfusion-dependent MDS patient populations. We're in the final stages of commercial readiness execution, which has included bringing on a sales force in April 2024. We're also engaging in marketing, commercial access, payer and reimbursement preparatory efforts, just as we are completing the build-out of our enterprise capabilities and systems to support our transition to a commercial stage company in short we're building on our momentum, acting with urgency and fully confident in our readiness for U.S. launch on potential approval. We're also financially well resourced to support the planned U.S. commercial launch with approximately $465 million on the balance sheet as of March 31st of this year, on the heels of a highly positive Modec outcome, we raised approximately $141 million in net proceeds from an underwritten public offering of common stock and a prefunded warrant. This offering included participation from RA Capital, Fairmont Bourbon that Farrell on adage Boxer, Vivo, deep track and multiple large investment management firms in addition to other new and existing investors from an EU perspective, we also have an MAA or marketing authorization application under review in this indication. If Imetelstat is approved by the European Commission, we expect a commercial launch in Europe would occur in 2025. We're continuing to evaluate our strategic options for European commercialization, including self commercialization or partnering and expect to provide an update later this year.

謝謝大家，大家早安。感謝您加入我們。我們準備在美國成功推出 imetelstat，用於治療低風險 MDS 患者的輸血依賴性貧血。如果獲得批准，我們非常高興有機會為患者帶來我們認為重要且差異化的藥物，我們的 PDUFA 日期為 6 月 16 日。我們繼續與 FDA 密切合作，他們完成了對我們新藥申請的審查，作為 3 月 14 日 NDA 審查流程的一部分，FDA 腫瘤藥物諮詢委員會或柯達以 12 比 2 投票支持臨床獲益風險概況與Imetelstat 一起用於低風險MDS 的預期適應症。訂單積壓反映出對 imetelstat 的強烈支持，也得到了低風險 MDS 社群的評論。在公共論壇上，血液學家和患者都談到了這種疾病中輸血依賴性貧血的負擔以及對新療法的需求，特別是對於難以治療的亞型患者，例如高輸血負擔和 RS 陰性患者。Imetelstat 具有獨特的優勢，可以解決這些服務不足的依賴輸血的 MDS 患者群體。我們正處於商業準備執行的最後階段，其中包括於 2024 年 4 月組建銷售團隊。我們也致力於行銷、商業准入、付款人和報銷準備工作，就像我們正在完成企業能力和系統的構建以支持我們向商業階段公司的過渡一樣，簡而言之，我們正在鞏固我們的勢頭，採取緊急行動，並對我們在美國可能獲得批准的發射做好準備充滿信心。我們還擁有充足的財務資源來支持計劃中的美國商業發布，截至今年3 月31 日，資產負債表上的資產負債表約為4.65 億美元，在Modec 取得非常積極的成果之後，我們從一個項目中籌集了約1.41 億美元的淨收益。此次發行包括RA Capital、Fairmont Bourbon that Farrell on adage Boxer、Vivo、deep track 和多家大型投資管理公司的參與，除了來自歐盟角度的其他新投資者和現有投資者外，我們還有正在審查的MAA 或行銷授權申請在此指示中。如果 Imetelstat 獲得歐盟委員會的批准，我們預計將於 2025 年在歐洲進行商業推出。我們正在繼續評估我們在歐洲商業化的策略選擇，包括自我商業化或合作，並預計在今年稍後提供更新。

I'd like to turn briefly to our ongoing clinical development efforts in Jackie relapsed and refractory MF patients. As many of you will recall, impact MF is the only Phase three MS study with overall survival as the primary endpoint last month, the Data Monitoring Committee evaluated unblinded data and recommended the clinical trial continued. In addition, the company reviewed enrollment rate and blinded death rates, which are lower than anticipated based on the initial planning assumptions. Accordingly, we're updating our guidance to extend the time lines by half a year with the interim analysis now expected in early 2026. And the final analysis expected in early 2027. We have the trial investigators remain excited about this study and the potential of a treatment that could improve survival for these patients who currently have very few treatment options and dismal survival. Dave will provide more color on this trial later in the call.

我想簡單介紹一下我們針對 Jackie 復發性和難治性 MF 患者正在進行的臨床開發工作。你們中的許多人都記得，影響 MF 是唯一以總生存期作為主要終點的三期 MS 研究，上個月，數據監測委員會評估了非盲數據並建議繼續進行臨床試驗。此外，該公司還審查了入學率和盲法死亡率，這些數據低於基於最初規劃假設的預期。因此，我們正在更新我們的指南，將時間軸延長半年，目前預計將在 2026 年初進行中期分析。最終分析預計在 2027 年初。我們的試驗研究人員對這項研究以及一種治療方法的潛力仍然感到興奮，這種治療方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。戴夫將在稍後的電話會議中提供有關此試驗的更多資訊。

Before I turn the call over to the team, I'd like to take a moment to reflect on how inspired I've been by all of our German people. Their passion for bringing our medicine to patients is palpable and drives our culture from our longest tenured colleagues who worked on the imetelstat IMD. to our sales force that joined us just a few weeks ago. There is a deeply shared sense of purpose that each one of us can meaningfully contribute to improving the lives of patients with hematologic malignancies. I believe that this Unity around our mission drives our urgency and collaboration, and it's a critical factor in transforming our fast-growing organization into a successful commercial company.

在將電話轉交給團隊之前，我想花點時間思考我們所有德國人民帶給我的啟發。他們將我們的藥物帶給患者的熱情是顯而易見的，並推動了我們在 imetelstat IMD 工作時間最長的同事的文化。致幾週前加入我們的銷售人員。我們每個人都有一種深刻的共同使命感，即我們每個人都可以為改善血液惡性腫瘤患者的生活做出有意義的貢獻。我相信，這種圍繞著我們使命的團結推動了我們的緊迫感和協作，這是將我們快速發展的組織轉變為成功的商業公司的關鍵因素。

With that, I'm going to turn the call over to Aneel for a commercial update. And Neil.

有了這個，我將把電話轉給 Aneel 以獲取商業更新。還有尼爾。

Thanks, Chip, and good morning to everyone. On the call, we believe that we are positioned very well for commercial value creation and are well prepared to execute a successful U.S. launch upon potential approval.

謝謝奇普，大家早安。在電話會議上，我們相信我們在創造商業價值方面處於非常有利的位置，並已準備好在獲得潛在批准後在美國成功推出。

As Jeff mentioned, in April, we completed the build-out of our full commercial organization with the hiring of our sales force, which has been now integrated and trained so that they will be prepared to be deployed in the field upon potential approval. I've had the privilege of getting to know this team really well, and I'm deeply impressed by their caliber experience and commitment. We also have commercial supply arrangements in place and have finalized our specialty distribution network and third party logistics. From a market perspective, we have work to identify the concentrated low-risk MDS prescriber base and our patient access and affordability solutions are on target for implementation at launch to support our launch preparation and commercial strategy, we have collected extensive market insights, which suggests that imetelstat is highly differentiated in this transfusion dependent low risk MDS market. Our research has shown that medical and payer stakeholders are dissatisfied with available options in the low-risk MDS space, which we believe creates an opportunity for imetelstat. Additionally, they expressed enthusiasm for the totality of clinical benefit seen that imetelstat, including durable red blood cell transfusion independence, hemoglobin increases and reduction in transfusion burden balanced with a generally well-characterized and manageable safety profile.

正如傑夫所提到的，四月份，我們透過僱用銷售人員完成了完整商業組織的建設，銷售人員現在已完成整合和培訓，以便他們準備好在潛在批准後部署到現場。我有幸非常了解這個團隊，他們的豐富經驗和奉獻精神給我留下了深刻的印象。我們也制定了商業供應安排，並最終確定了我們的專業分銷網絡和第三方物流。從市場角度來看，我們努力確定集中的低風險MDS 處方者基礎，我們的患者獲取和負擔能力解決方案的目標是在啟動時實施，以支持我們的啟動準備和商業策略，我們收集了廣泛的市場見解，這顯示imetelstat 在這個輸血依賴性低風險 MDS 市場中具有高度差異化。我們的研究表明，醫療和支付方利害關係人對低風險 MDS 領域的可用選擇不滿意，我們認為這為 imetelstat 創造了機會。此外，他們對 imetelstat 的整體臨床益處表示熱情，包括持久的紅血球輸注獨立性、血紅蛋白增加和輸血負擔減少，與整體上良好表徵和易於管理的安全性相平衡。

Lastly, from a patent and regulatory exclusivity perspective in the US, as shown at the end of the slide that we are using today, we have orphan drug exclusivity through first half 2031 for MDS. Our method of use patent for MDS and MF expires in March 2033. But if the patent term extension is applied to this use patent. We expect exclusivity would be extended to 2037 and would apply to all uses covered by the backend, including both MDS and AML. We believe Imetelstat is uniquely positioned to address unmet needs in transfusion dependent low risk MDS as captured on this slide, which depicts the treatment landscape as well as a simplified schematic, reflecting the current NCCN guidelines for MDS. As you may be aware, the NCCN guidelines, along with published results from the randomized trials remain among the most important factors that influence clinical and payer pathways and significantly inform prescribing behavior. The NCCN guidelines recommend ESA's as the preferred treatment option, but the largest segment of frontline RS negative patients. It's important to remember that many of these patients will show a loss of response to ESA treatment in the frontline setting in approximately 18 to 24 months. There also continues to be limited treatment options for patients with serum EPO levels greater than 500 milligrams per year and participation in clinical trials for ESA ineligible. Rs negative patients is encouraged by NCCN guidelines from our perspective, these guidelines reflect a lack of effective treatment options, in particular, for those patients who are ESA ineligible, high transfusion burden patients and for RS negative lower-risk MDS patients constitute approximately 75% of the market. This is a need we believe imetelstat can powerfully address as a potentially durable treatment that can be used broadly across MDS subtypes. This next slide summarizes our latest market research from 2024 of 50 community and academic U.S. hematologists. When surveyed about the product profile of imetelstat and what factors may drive treatment decisions it additionally reflects fair priorities in the lower-risk MDS. Our findings show that these physicians know that achievement of RBCPI. and rise in hemoglobin are two key factors that drives their decision making for them. They point to the greater than 24 week TI. and patient-reported outcome data from EMERGE as essential considerations. These physicians view imetelstat as a likely standard of care across the relapsed refractory RS negative patient population expressing enthusiasm for the significant efficacy improvement in a population with limited current treatments. These physicians also note transfusion burden has strong impact on treatment decisions and believe Imetelstat is a compelling option for patients with high transfusion burden due to differentiated data in this patient population.

最後，從美國專利和監管獨佔權的角度來看，正如我們今天使用的幻燈片末尾所示，我們在 2031 年上半年之前對 MDS 擁有孤兒藥獨佔權。我們的 MDS 和 MF 使用方法專利將於 2033 年 3 月到期。但如果對該使用專利申請專利期限延長。我們預計排他性將延長至 2037 年，並將適用於後端涵蓋的所有用途，包括 MDS 和 AML。我們相信，Imetelstat 具有獨特的優勢，可以解決輸血依賴性低風險MDS 中未滿足的需求，如這張幻燈片所示，該幻燈片描繪了治療前景以及簡化的示意圖，反映了當前NCCN 的MDS 指南。您可能知道，NCCN 指南以及已發表的隨機試驗結果仍然是影響臨床和付款途徑並為處方行為提供重要資訊的最重要因素之一。NCCN 指引推薦 ESA 作為首選治療選擇，但第一線 RS 陰性患者的比例最大。重要的是要記住，這些患者中的許多人將在大約 18 至 24 個月內對前線環境中的 ESA 治療失去反應。對於血清 EPO 水平每年超過 500 毫克且不符合 ESA 臨床試驗資格的患者，治療選擇仍然有限。從我們的角度來看，NCCN 指南鼓勵 RS 陰性患者，這些指南反映了缺乏有效的治療方案，特別是對於那些不符合 ESA 資格的患者、高輸血負擔患者和 RS 陰性低風險 MDS 患者約佔 75%市場的。我們相信 imetelstat 可以有力地解決這一需求，作為一種潛在的持久治療方法，可以廣泛用於 MDS 亞型。下一張投影片總結了我們對 50 位美國社區和學術血液學家進行的 2024 年最新市場研究。當對 imetelstat 的產品概況以及可能推動治療決策的因素進行調查時，它也反映了低風險 MDS 的公平優先事項。我們的研究結果表明，這些醫生知道 RBCPI 的成就。和血紅蛋白的升高是推動他們做出決策的兩個關鍵因素。他們指出了超過 24 週的 TI。以及來自 EMERGE 的患者報告的結果數據作為重要考慮因素。這些醫生認為 imetelstat 可能是復發難治性 RS 陰性患者群體的一種可能的護理標準，並對目前治療有限的人群中顯著提高療效表示熱情。這些醫生也指出，輸血負擔對治療決策有很大影響，並相信伊美司他對於高輸血負擔患者來說是一個令人信服的選擇，因為該患者群體的數據存在差異。

The imetelstat profile also resonates with payer priorities and they recognize the unmet need in the transfusion dependent, low-risk MDS space. They express that NCCN guideline inclusion and peer review publications. I've seen as important evidence for their consideration. Inclusion in the NCCN guidelines requires an FDA label as well as the publication of the pivotal data, which is already available in the long-term once potential FDA approval is secured. Our teams stand ready to engage with NCCN to begin the process of updating their guidelines. It's important to note that given the elderly patient population with transfusion-dependent, lower-risk MDS the majority of US patients are expected to be treated under the Medicare Part D setting. We are confident patients will have broad access to imetelstat. We expect to see imetelstat uptake across ESA ineligible, ESA failed RS negative and RS positive high transfusion burden patients based on our latest 2024 market research of 50 US-based practicing hematologists across both community and academic settings.

imetelstat 的概況也與付款人的優先事項產生共鳴，他們認識到輸血依賴性、低風險 MDS 領域未滿足的需求。他們表示 NCCN 指南納入和同行評審出版物。我認為這是他們考慮的重要證據。納入 NCCN 指南需要 FDA 標籤以及關鍵數據的公佈，一旦獲得 FDA 潛在批准，這些數據就已經可以長期使用。我們的團隊隨時準備與 NCCN 合作，開始更新其指南。值得注意的是，考慮到患有輸血依賴性、低風險 MDS 的老年患者群體，大多數美國患者預計將在 Medicare D 部分環境下接受治療。我們相信患者將能夠廣泛使用 imetelstat。根據我們對 50 名美國社區和學術機構的執業血液學家進行的最新 2024 年市場研究，我們預計在 ESA 不合格、ESA 失敗的 RS 陰性和 RS 陽性高輸血負擔患者中採用 imetelstat。

On the left-hand side of this slide, you can see that our market research suggests meaningful imetelstat use in frontline ESA ineligible patients, especially those who are RS negative. The right-hand side of the slide shows the estimated second-line population, approximately 90% of which are expected to be ESA or luspatercept experienced. Our market research suggests a broad use of imetelstat across the second line, regardless of frontline therapy, particularly for RS negative patients, as you can see on the figures on the right, which are further segmented for RS positive and RS negative patients within these subgroups. Our findings confirm the significant unmet need across the lower-risk MDS patient population. And we strongly believe that imetelstat is approved, can play a meaningful role in the treatment paradigm of transfusion dependent lower risk MDS.

在這張投影片的左側，您可以看到我們的市場研究表明，對於不符合 ESA 資格的第一線患者，特別是 RS 陰性的患者，有意義地使用 imetelstat。幻燈片右側顯示了估計的二線人群，其中大約 90% 預計有 ESA 或 luspatercept 經驗。我們的市場研究表明，無論一線治療如何，imetelstat 都會在第二線廣泛使用，特別是對於 RS 陰性患者，如右圖所示，這些亞組中進一步細分為 RS 陽性和 RS 陰性患者。我們的研究結果證實了低風險 MDS 患者群體的顯著未滿足需求。我們堅信，imetelstat 已獲得批准，可以在輸血依賴性低風險 MDS 的治療模式中發揮有意義的作用。

Moving forward, we believe we are well positioned to capitalize on imetelstat opportunity in transfusion-dependent, lower-risk MDS by building on the unique product profile and executing on the launch critical success factors that are driving our commercial plan.

展望未來，我們相信，透過建立獨特的產品概況並執行推動我們商業計劃的推出關鍵成功因素，我們能夠充分利用 imetelstat 在輸血依賴性、低風險 MDS 領域的機會。

From a prescriber perspective, we have a few important goals that prescribers embrace the totality of clinical benefit achievable with imetelstat and understand the efficacy profiles across MDS subgroups, including RS negative and high transfusion burden patients. It's also critical that we provide education and support for physicians on the imetelstat safety profile and help them to contextualize and manage cytopenias so they can offer and optimize patient experience and duration of effect. This support will also help prescribers have a good first experience with imetelstat, which is another important cause from a patient access perspective as reflected by our research, the need for new treatment options and the high unmet need populations that imetelstat can address are expected to be important considerations to drive access and reimbursement. We are honored and privileged to have the opportunity to launch a medicine that could have such significant, meaning for transfusion dependent, lower risk MDS patients and their families, and we are deeply energized to embark on this journey.

從處方者的角度來看，我們有幾個重要的目標，即處方者接受 imetelstat 可實現的全部臨床益處，並了解 MDS 亞群（包括 RS 陰性和高輸血負擔患者）的療效概況。同樣重要的是，我們為醫生提供有關 imetelstat 安全性的教育和支持，並幫助他們了解和管理血球減少症，以便他們能夠提供和優化患者體驗和效果持續時間。這種支持還將幫助處方者對imetelstat 獲得良好的初次體驗，這是從患者可及性角度來看的另一個重要原因，正如我們的研究所反映的那樣，對新治療方案的需求以及imetelstat 可以解決的高未滿足需求人群預計將是推動獲取和報銷的重要考慮因素。我們很榮幸有機會推出一種對輸血依賴、低風險 MDS 患者及其家人具有如此重大意義的藥物，我們充滿活力地踏上這趟旅程。

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

這樣，我會將電話轉給費伊，以了解醫療和臨床最新情況。

Okay. Thanks, Michelle, and thanks, everyone, for joining our call today. As Tim mentioned, on March 14, the FDA Oncologic Drugs Advisory Committee voted 12 to 2 in favor of the clinical benefit risk profile of imetelstat in transfusion dependent, lower risk MDS indication proposed in our MDS. All that considered the results from our Phase three IMerge trial as well as the unmet need and limited available treatment options for patients with this cancer. Needless to say, we are very pleased with the committee's decision to recognize the positive clinical benefit risk profile of imetelstat for the treatment of transfusion dependent anemia in adult patients with lower risk MDS, as Chip mentioned in the public forum provided a critical opportunity for the Autodesk to hear from members of the lower risk MDS community, including hematologists, patient advocates and patients. Throughout the testimony, there were several central themes that deeply resonates with me as a hematologist experience in treating lower risk MDS patients.

好的。謝謝米歇爾，謝謝大家今天加入我們的電話會議。正如 Tim 所提到的，3 月 14 日，FDA 腫瘤藥物諮詢委員會以 12 比 2 的投票結果支持我們的 MDS 中提出的 imetelstat 在輸血依賴性、低風險 MDS 適應症中的臨床獲益風險概況。所有這些都考慮了我們第三階段 IMerge 試驗的結果以及這種癌症患者未滿足的需求和有限的可用治療選擇。不用說，我們對委員會決定認可 imetelstat 用於治療低風險 MDS 成年患者輸血依賴性貧血的積極臨床獲益風險狀況感到非常高興，正如 Chip 在公共論壇中提到的那樣，這為Autodesk 將聽取低風險MDS 社群成員的意見，包括血液學家、病患權益倡導者和病患。在整個證詞中，有幾個中心主題與我作為血液科醫生治療低風險骨髓增生異常綜合徵患者的經驗產生了深刻的共鳴。

Patient events also echo what we hear in our market research and at medical conferences, the profoundly negative impact of anemia and transfusion dependence on the quality of life for both patients and their families were strikingly evident. These patients are chronically fatigued and struggle to keep up with their daily activities, commonly resulting in like a social and emotional burden, lower-risk MDS and the progressive disease. And by the time, the patients progress to transfusion dependence, they do not have many treatment options. In fact, hematologists at the Kodak pointed out that they usually end up cycling through most or all of their options making an additional treatment in their armamentarium potentially practice-changing. There was also significant discussion around the deep meaningfulness of RBC transfusion independence for these patients, one of whom testified at the low deck that she believed transfusion independence would give us more time to have a better quality of life. A nurse commented in public hearing that time not spent in an infusion chair time and living for daily living from a clinical perspective. While transfusions can provide short-term relief. They can also cause long-term consequences. Frequent red blood cell transfusions can leak Alan utilization and difficulty in identifying a matched donor to support the continuous transfusion need over time. Patients can develop end organ dysfunction due to iron overload. This is in addition to the psycho social and emotional toll that transfusion dependence can take on patients, the hematology and patient communities expressed that beyond durable RBC TI., the hemoglobin increases and reduction in transfusion burden observed with Imetelstat are important indicators of clinical benefit.

患者事件也與我們在市場研究和醫學會議上聽到的情況相呼應，貧血和輸血依賴對患者及其家人的生活品質產生的深遠負面影響非常明顯。這些患者長期疲勞，難以跟上日常活動，通常會導致社交和情緒負擔、低風險 MDS 和進行性疾病。當患者發展為輸血依賴時，他們沒有太多的治療選擇。事實上，柯達的血液學家指出，他們通常最終會循環使用大部分或全部選擇，在他們的醫療設備中進行額外的治療可能會改變實踐。關於紅血球輸血獨立性對這些患者的深刻意義也進行了重要討論，其中一位患者在底層作證說，她相信輸血獨立性將使我們有更多時間獲得更好的生活品質。一位護理師在公開聽證會上評論說，從臨床角度來看，時間不是花在輸液椅上的時間，而是為了日常生活而生活。雖然輸血可以提供短期緩解。它們還會造成長期後果。頻繁的紅血球輸注可能會導致艾倫的利用率下降，並且難以識別匹配的捐贈者來支持隨著時間的推移持續輸血的需求。患者可能因鐵過量而出現終末器官功能障礙。除了輸血依賴可能對患者帶來的心理社會和情感損失外，血液學和患者社區表示，除了持久的紅血球TI之外，使用伊美司他觀察到的血紅蛋白增加和輸血負擔減少是臨床獲益的重要指標。

Lastly, several hematologists spoke at their comfort level managing cytopenias, given their familiarity with these hematologic toxicities and the side effect of many medicines regularly used in clinical practice. This reinforces our belief that with the proper context and education these cytopenias should be able to be well managed by hematologists in a real-world setting. Overall hematologist patient advocates and patients express support for new treatment options in transfusion dependent, lower risk MDS, especially for treatment with the durability of our BCTI. team with imetelstat.

最後，幾位血液學家在處理血球減少症方面發表了自己的看法，因為他們熟悉這些血液學毒性以及臨床實踐中經常使用的許多藥物的副作用。這強化了我們的信念，即透過適當的背景和教育，血液學家應該能夠在現實世界中很好地管理這些血球減少症。總體而言，血液科醫生患者倡導者和患者均表示支持輸血依賴性、低風險 MDS 的新治療方案，特別是具有我們 BCTI 持久性的治療方案。與 imetelstat 合作。

Turning next to our medical affairs readiness. To support our expected launch, we have a highly skilled medical affairs team in place. This team has been instrumental in conducting peer-to-peer scientific exchange of medical information, particularly the medical congresses and publications awareness, not in the cost side of the hematology community has been heightened by your presence at congresses like E. half and ASH and particularly by the publication of Phase three EMERGE data in The Lancet last year, our medical affairs team will partner with our commercial colleagues on the important effort to have imetelstat included in NCCN Guidelines once it is approved.

接下來談談我們的醫療事務準備。為了支持我們的預期發布，我們擁有一支高技能的醫療事務團隊。團隊在進行醫學資訊的點對點科學交流方面發揮了重要作用，特別是醫學大會和出版物的意識，而不是在血液學界的成本方面，您參加E. half 和ASH 等大會提高了血液學界的成本方面特別是去年在《柳葉刀》上發表第三階段 EMERGE 數據後，我們的醫療事務團隊將與我們的商業同事合作，共同努力，一旦 imetelstat 獲得批准，將其納入 NCCN 指南。

Lastly, our field medical colleagues are in place and are prepared to be a critical resource in helping support physicians in managing their lower risk MDS patients.

最後，我們的現場醫療同事已就位，並準備好成為幫助支持醫生管理低風險 MDS 患者的關鍵資源。

Turning now to our Phase three impact MF trial of imetelstat inject inhibitor relapsed refractory MF. We are proud to sponsor the first and only Phase three trial in MS that has overall survival as its primary endpoint by a total of 320 patients are planned to be enrolled into two to one randomization for the imetelstat arm versus the best available treatment arm per protocol. Interim analysis has been planned and about 35% of the planned enrolled patients have died. And the final analysis, when approximately 50% of the planned enrolled patient contacts as an overall survival study, the time line for the interim and final analysis is dependent not only on the rate of enrollment, but also on the event rate for patient death rate in the trial. The data monitoring committee evaluated unblinded data last month and recommended the study continue. In addition, we reviewed enrollment rates and blended gas rates, which are lower than anticipated in our initial planning assumptions. Accordingly, we are updating our guidance to extend the timelines by half of the year and now expect the interim analysis in early 2026 and the final analysis in early 2027 because the factors affecting these estimates are highly variable and difficult to predict. The actual interim and final analysis could occur sooner or later than we currently expect as the trial continues we'll continue to monitor enrollment and death rates and update guidance if appropriate. Of note, we have multiple ongoing work streams to increase trial enrollment. Our clinical operations team has been conducting on-site visits to clinical trial sites around the globe. Additionally, we have been increasing our engagement with patient advocacy groups in the myelofibrosis disease space. I think it's important to note that we at Geron as well as the impact MS trial investigators and also patient advocates continue to express excitement around the potential to extend survival in this Jack inhibitor relapse refractory population by treatment of myelofibrosis is dominated by Jack inhibitors or therapies and other mechanisms of action in combination with Check inhibitors when patients become unresponsive to Jack 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 patients.

現在轉向我們的 imetelstat 注射抑制劑復發難治性 MF 的第三階段影響 MF 試驗。我們很自豪能夠贊助第一個也是唯一一個以總生存期為主要終點的多發性硬化症三期試驗，計劃將總共320 名患者納入imetelstat 組與每個方案的最佳可用治療組的二比一隨機分組。中期分析已計劃進行，計劃納入的患者中約 35% 已死亡。最終分析，當大約 50% 的計劃入組患者接觸作為總體生存研究時，中期和最終分析的時間線不僅取決於入組率，還取決於患者死亡率的事件率在審判中。數據監測委員會評估了上個月的非盲數據，並建議繼續進行研究。此外，我們還審查了入學率和混合汽油費率，這些比率低於我們最初規劃假設中的預期。因此，我們正在更新我們的指導意見，將時間表延長一半，現在預計中期分析將在 2026 年初進行，最終分析將在 2027 年初進行，因為影響這些估計的因素變化很大且難以預測。隨著試驗的繼續，實際的中期和最終分析可能會比我們目前預期的早或晚發生，我們將繼續監測入組率和死亡率，並在適當的情況下更新指南。值得注意的是，我們有多個正在進行的工作流程來增加試驗註冊人數。我們的臨床營運團隊一直在對全球各地的臨床試驗地點進行現場考察。此外，我們一直在加強與骨髓纖維化疾病領域患者倡導團體的接觸。我認為值得注意的是，我們Geron 以及影響MS 試驗研究者和患者倡導者繼續對通過以Jack 抑製劑或療法為主的骨髓纖維化治療來延長Jack 抑製劑復發難治性人群的生存期的潛力表示興奮當患者對 Jack 抑制劑無反應時，將其他作用機制與 Check 抑制劑合併使用，這會導致約 75% 的患者在五年後停止治療。他們面臨著大約 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，它可能會改變這些患者的治療方法。

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

這樣，我會將電話轉給米歇爾，了解最新的財務狀況，這會有所幫助。

Thanks, Phil, and good morning, everyone for details Q1 2024 financials. Please refer to the press release we issued this morning, which is available on our website.

謝謝菲爾，大家早上好，了解 2024 年第一季財務狀況的詳細資訊。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。

Now let me bring your attention to a few highlights from the quarter. As of March 31, 2024, the Company had approximately $465 million in cash and marketable securities, including proceeds from an underwritten public offering of common stock and a prefunded warrant in March 2024 for net proceeds of approximately $141 million. Total operating expenses for the first quarter of 2024 were $56.4 million compared to $40.1 million for the same period in 2023. Research and development expenses for the first quarter of 2024 were $29.4 million compared to $27.2 million for the same period in 2023. The increase year over year primarily reflects higher CMC costs due to the timing of imetelstat commercial manufacturing batches and increased personnel-related expenses for additional headcount.

現在讓我提請您注意本季的一些亮點。截至 2024 年 3 月 31 日，本公司擁有約 4.65 億美元的現金和有價證券，包括 2024 年 3 月承銷的公開發行普通股和預融資認股權證的收益，淨收益約為 1.41 億美元。2024 年第一季的總營運費用為 5,640 萬美元，而 2023 年同期為 4,010 萬美元。2024 年第一季的研發費用為 2,940 萬美元，而 2023 年同期為 2,720 萬美元。同比增長主要反映了由於 imetelstat 商業生產批次的時間表以及增加人員而增加的人員相關費用導致 CMC 成本增加。

G&a expenses for the first quarter of 2024 were $27.1 million compared to $12.9 million for the same period in 2023. The increase primarily reflects our investment in commercial preparatory activities and higher personnel-related expenses for additional headcount as we have been preparing to transition from a clinical to commercial stage company as of March 31, 2024 and prior to adding our sales force. In April, we had 162 full-time employees subject to approval of imetelstat in the US. We plan to grow to a total of approximately 250 to 300 employees by year end 2024. Our projected full year 2024 operating expenses are expected to be between $270 million and $280 million based on our current operating plans and our assumptions regarding the timing of the potential approval and commercial launch of imetelstat and TDLR. MDS in the US. We believe that our existing cash, cash equivalents and current and noncurrent marketable securities, together with our projected revenues from US sales of imetelstat is approved potential proceeds from the exercise of warrants and warrants and future drawdowns under our loan facility will be sufficient to support our operations into the second quarter of 2026.

2024 年第一季的一般管理費用為 2,710 萬美元，而 2023 年同期為 1,290 萬美元。這一增長主要反映了我們對商業準備活動的投資以及因增加員工人數而增加的人員相關費用，因為我們一直在準備從2024 年3 月31 日起以及在增加銷售人員之前從臨床階段公司過渡到商業階段公司。4月份，我們有162名全職員工接受美國imetelstat的批准。我們計劃在 2024 年底將員工總數增加到約 250 至 300 名。根據我們目前的營運計劃以及我們對 imetelstat 和 TDLR 的潛在批准和商業推出時間的假設，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。美國MDS。我們相信，我們現有的現金、現金等價物以及當前和非流動的有價證券，加上我們在美國銷售imetelstat 的預計收入已獲得批准，行使認股權證和認股權證的潛在收益以及我們貸款安排下的未來提款將足以支持我們營運至 2026 年第二季。

I will now turn the call back over to Chip.

我現在將把電話轉回給奇普。

Thanks, Michelle. We believe imetelstat has the potential to offer a life-changing treatment option for patients with transfusion dependent lower risk MDS building on the momentum from the resoundingly positive Modec were deeply energized and well prepared to launch imetelstat in the U.S. If approved, driven by our experienced leaders and expected excellent execution. We feel confident in our ability to capitalize on this robust opportunity and to transform Geron into a successful commercial company. We believe this transformation will create significant value for patients and shareholders let let's now open the line to questions. Operator?

謝謝，米歇爾。我們相信 imetelstat 有潛力為輸血依賴性低風險 MDS 患者提供改變生活的治療選擇，Modec 非常積極，並做好了在美國推出 imetelstat 的準備。出色的執行力。我們對利用這一強勁機會並將 Geron 轉變為成功的商業公司的能力充滿信心。我們相信這項轉變將為患者和股東創造巨大的價值，現在讓我們開始提問。操作員？

Thank you. The floor is now open for questions. If you have dialed in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again, if you are called upon to ask a question and are listening via loud speaker on your device, please pick up your handset to ensure that your phone is not on mute. When asking your question, your first question comes from the line of Tara Bancroft, TD Cowen. Your line is open.

謝謝。現在可以提問。如果您已撥入並想提問，請按下電話鍵盤上的星號一舉手並加入隊列。如果您想撤回您的問題，只需再次按星號一即可，如果您被要求提問並且正在透過裝置上的揚聲器收聽，請拿起您的聽筒以確保您的手機未處於靜音狀態。當你提出問題時，你的第一個問題來自 Tara Bancroft, TD Cowen。您的線路已開通。

Hi, good morning and thanks so much for taking the questions. So mine is on regarding the myelofibrosis trial timelines. Can you comment on if it was more so due to slower enrollment or if there was a heavier impact from having fewer events than anticipated? And if it's the latter. Can you remind us of the bar here and maybe if your expectations have changed for where OS. could land for the control? Like how should we think about expectations here. Thanks.

你好，早安，非常感謝你提出問題。所以我的重點是關於骨髓纖維化試驗的時間表。您能否評論一下，這種影響是否更大是因為註冊速度較慢，還是因為活動數量比預期少而造成的影響更大？而如果是後者的話。您能否提醒我們這裡的酒吧，也許您對作業系統的期望已經改變。可以著陸控制嗎？就像我們應該如何考慮這裡的期望。謝謝。

And I'm sorry, go ahead. I'll take that, please. They are you off mute.

抱歉，請繼續。請我接受。他們讓你保持沉默。

I'll apologize, new issues. And in my comments, the enrollment and death rates are both lower than anticipated, and we are not able to provide additional detail into which ones the driving force. And as you noted, that pushes the timelines out about six months. We did see continued enthusiasm for the study, and we'll continue to monitor and update and as appropriate.

我會道歉，新問題。在我的評論中，入學率和死亡率都低於預期，我們無法提供更多細節來說明哪些因素是驅動力。正如您所指出的，這將時間表推遲了大約六個月。我們確實看到了人們對這項研究的持續熱情，我們將繼續酌情進行監控和更新。

Okay. Thank you.

好的。謝謝。

Thanks, Dan.

謝謝，丹。

Your next question comes from the line of Karin JOHNSON of Goldman Sachs. Your line is open.

你的下一個問題來自高盛的 Karin JOHNSON。您的線路已開通。

Good morning. This is Greg on for Karin. So first one from us. Have you all initiated labeling discussions with FDA of imetelstat in Burress myelodysplastic syndrome?

早安.這是卡琳的格雷格。這是我們的第一個。你們是否已經開始與 FDA 就 imetelstat 治療 Burress 骨髓增生異常症候群的標籤進行討論？

Yes. So we've received pretty smooth, Craig. We've received comments from the FDA on our on our draft label. However, as you would imagine, the FDA hasn't yet completed its review so we certainly look forward to continuing our conversations with the agency as we approach the data. But we do not expect to publicly disclose or discuss any ongoing regulatory interactions with the division prior to private producers.

是的。所以我們的進展非常順利，克雷格。我們已收到 FDA 對我們的標籤草案的評論。然而，正如您所想像的那樣，FDA 尚未完成審查，因此我們當然期待在處理數據時繼續與該機構進行對話。但我們預計不會先於私人生產商公開披露或討論與該部門正在進行的任何監管互動。

Got it. That makes a lot of sense. And it seems like from the commercial standpoint and clinical standpoint that getting NCCN Guidelines updated is a top priority. So how quickly do you think that could occur following the potential approval of imetelstat?

知道了。這很有意義。從商業角度和臨床角度來看，更新 NCCN 指南似乎是重中之重。那麼，您認為在 imetelstat 獲得批准後，這種情況會多快發生？

And Neil, can you take that one short pause?

尼爾，你能稍微停一下嗎？

So Greg, we are able to provide an official submission to NCCN upon approval, which we are ready to do. So. This obviously includes the approved prescribing information or the label. It includes the peer-reviewed publication Lancet, which exists and it includes our cover letter, highlighting the patient populations. Typically NCCN update the guidelines within two to three months for new drugs that are received for low-risk MDS within the NCCN, low-risk MDS committee. So our expectation is if we submit in June upon approval about two to three months later, we would expect to see the guidelines reflect imetelstat.

因此，Greg，我們能夠在獲得批准後向 NCCN 提供正式提交材料，我們已經準備好這樣做。所以。這顯然包括批准的處方資訊或標籤。它包括同行評審的出版物《柳葉刀》，該出版物已存在，並且包括我們的求職信，強調了患者群體。通常，NCCN 會在兩到三個月內更新 NCCN 低風險 MDS 委員會內針對低風險 MDS 收到的新藥的指南。因此，我們的期望是，如果我們在六月提交並在大約兩到三個月後獲得批准，我們希望看到該指南反映 imetelstat。

Got it. Thank you so much.

知道了。太感謝了。

Your next question comes from the line of Gil Blum of Needham & Company. Your line is open.

您的下一個問題來自 Needham & Company 的 Gil Blum。您的線路已開通。

Hi, good morning, everyone, and thanks for taking the questions. Maybe a slightly different tack on my list fibrosis. So were there changes to the standard of care over the last couple of years that may explain some of this slower accumulation and secondly, can you comment on what the challenges are for enrollment and competition from commercial treatments, other studies, whatever information you could provide? Thank you.

大家早安，感謝您提出問題。也許我的纖維化清單上的策略略有不同。那麼，過去幾年護理標準是否發生了變化，這可以解釋這種緩慢積累的一些原因，其次，您能否評論一下商業治療、其他研究以及您可以提供的任何信息在招生和競爭方面面臨的挑戰是什麼？謝謝。

Elekta pay, take it first and I'll address it if necessary and go ahead.

醫科達付款，先拿走，如有必要我會解決並繼續。

Thanks for the question. Got plenty of Durbin and indeed, we've had the approval of <unk> few more Jack inhibitors over the last couple of years. I do believe that has impacted the enrollment rate excuse me a couple, but it is multifactorial, including the new approvals of Jack inhibitors, the lack of Jack inhibitor treatment option in the BAT arm and even still challenges of resourcing issues at site and staffing. So all of these contribute to the lower enrollment rates that we predicted. And we then predicted, but we have not unanticipated and conditional amendment of the Bush.

謝謝你的提問。得到了大量的 Durbin，事實上，在過去的幾年裡，我們已經獲得了更多的傑克抑制劑的批准。我確實相信這影響了入學率，請原諒，但這是多因素的，包括 Jack 抑制劑的新批准、BAT 部門缺乏 Jack 抑制劑治療選擇，甚至現場資源和人員配置問題仍然存在挑戰。因此，所有這些都導致​​了我們預測的較低的入學率。然後我們就預測了，但是我們並沒有對布希進行無預期和有條件的修正。

All right. Thanks for the color.

好的。謝謝你的顏色。

Okay, thanks again, if you would like to ask a question, press star then followed by the number one on your telephone keypad.

好的，再次感謝，如果您想提問，請按星號，然後按電話鍵盤上的數字 1。

Your next question comes from the line of Stephen Willey of Stifel. Your line is open.

您的下一個問題來自 Stifel 的 Stephen Willey。您的線路已開通。

Hi, good morning, guys. This is Tony on for Steve. Thank you for taking my questions and congrats on the progress. And we have just two questions on our end. The first one is And regarding the launch preparation process for that coming on approval. So I mean that you definitely provided list of things that you guys have accomplished so far. So in terms of preparation, what are the major steps that need to be done and maybe like additional color on that. And the second question is related to just a follow up on the prior questions regarding MS trial. So is there. So would it be possible to provide any like number or percentage like percentage wise in terms of like our enrollment rate and John and also like what are the steps that you guys are actually taking in order to expedite enrollment? And what is your confidence level that you guys will not need to actually extend the extend the time line for interim and final analysis.

嗨，早上好，夥計們。這是東尼為史蒂夫代言。感謝您回答我的問題並祝賀我的進展。我們最後只有兩個問題。第一個是關於即將批准的啟動準備過程。所以我的意思是，你們確實提供了迄今為止你們所完成的事情的清單。那麼在準備方面，需要完成哪些主要步驟，也許還需要補充一些顏色。第二個問題與先前有關 MS 試驗的問題有關。那裡也是如此。那麼，是否有可能提供任何類似的數字或百分比，例如我們的入學率和約翰，以及你們為加快入學而實際採取的步驟？你們對不需要實際延長中期和最終分析的時間線的信心有多大？

Thank you. But so I'll take the first question on the launch preparations, and Neil will take that one. And then we'll I'll pivot over after that. To your follow question on the MF trial. Go ahead.

謝謝。但我將回答關於發射準備的第一個問題，尼爾將回答這個問題。然後我們會在那之後轉向。關於 MF 試驗的以下問題。前進。

Sorry. Sure. So thanks for the question on a really important step for us is the completion of the onboarding of our full commercial team. As we stated on our call, our key account managers in the field are also now fully onboarded, and we are working very hard towards our potential approval in June. Given our producer date, our concentration is both on ensuring that we have full commercial supply. Our distribution network is fully finalized. We are preparing all materials to inform stakeholders, including payers, our prescribers and to the populations that we interact with. We have identified the prescriber base. We are looking towards our access and affordability solutions. Everything remains on track and our expectation is a well-executed launch Quadrem. It'll start in the U.S. market upon approval.

對不起。當然。因此，感謝您提出的問題，對我們來說，真正重要的一步是完成我們整個商業團隊的入職。正如我們在電話會議中所說，我們在該領域的主要客戶經理現在也已全面入職，我們正在非常努力地爭取 6 月的批准。鑑於我們的生產日期，我們的重點是確保我們有充足的商業供應。我們的分銷網絡已經完全確定。我們正在準備所有資料，以告知利害關係人，包括付款人、我們的處方者以及與我們互動的人群。我們已經確定了處方者基礎。我們正在尋找可近性和可負擔性的解決方案。一切都保持在正軌上，我們期望 Quadrem 能夠順利發布。獲得批准後將在美國市場啟動。

It's got to name and then, hey, why don't you take the question on the follow-up question on the MF?

它必須命名，然後，嘿，為什麼不回答 MF 的後續問題呢？

Yes, thanks for the question. I'm going to try to remember all of the components regarding the enrollment rate we announced last year in November that the study was 50% enrolled and we plan to provide updates when it's material and and Enrollment is continuing.

是的，謝謝你的提問。我將嘗試記住有關我們去年 11 月宣布的註冊率的所有組成部分，該研究的註冊率為 50%，我們計劃在材料成熟且註冊仍在繼續時提供更新。

It is at a steady pace. As I mentioned before, enthusiasm has not really diminished for this study. So we continue to see movement of it. Remind me the other question.

它的步伐很穩定。正如我之前提到的，人們對這項研究的熱情並沒有真正減弱。所以我們繼續看到它的運動。提醒我另一個問題。

I can take it. I think that would yes. I think what she was getting at was sort of the in issue of how we would follow all of this going forward in might it be necessary to to refine further?

我可以接受。我想是的。我認為她想要表達的問題是我們將如何跟進這一切，是否有必要進一步完善？

Look, I think you said in your prepared comments that these estimates are really variable to pardon me and pretty difficult because you have two variables, right? You have an enrollment rate which and really cannot be seen as the only contributor to the time lines here. And we're as you heard, we're doing everything we can to keep that enrollment rate up and say commented in answer to a previous question on whether there was going to ask about to commercial it launches of other competing Jack products. She mentioned the fact that the and that we don't have a Jack inhibitor in the in the BAT arm and so forth. But I think the other side is the pace at which we accrue events, right? Does it ends and that's a lot harder to predict. And I'll just simply say because we do not and have not unblinded the study, of course, important to note, all we can look at is sort of the pace of those events. And I will remind everybody that the study is a two for one randomization. So I think we and we made the comment in the prepared remarks that we will have to follow along. And if things require further updates, either we go slower and in towards the interim and final analysis or we go faster, we'll certainly need to update but we don't make a specific commitment on exactly when we would do that. So I hope we'll continue to monitor both enrollment and event rates and update guidance as required.

聽著，我想你在準備好的評論中說過，請原諒我，這些估計確實是可變的，而且相當困難，因為你有兩個變量，對吧？您的入學率確實不能被視為對此處時間線的唯一貢獻者。正如您所聽到的，我們正在盡一切努力保持入學率上升，並在回答之前關於是否會詢問是否將其他傑克競爭產品的商業化推出的問題時發表評論。她提到了這樣一個事實，即我們的 BAT 臂中沒有 Jack 抑制劑等等。但我認為另一面是我們發生事件的速度，對嗎？它是否會結束，這很難預測。我只是簡單地說，因為我們沒有也沒有取消盲法研究，當然，值得注意的是，我們所能看到的只是這些事件的進展速度。我要提醒大家，這項研究是二對一的隨機化。因此，我認為我們在準備好的發言中發表了評論，我們必須遵循。如果事情需要進一步更新，要么我們放慢速度進行中期和最終分析，要么我們走得更快，我們當然需要更新，但我們不會具體承諾何時更新。因此，我希望我們將繼續監控註冊率和活動率，並根據需要更新指南。

So I hope that answers your question. Happy to take a follow on if needed,

所以我希望這能回答你的問題。如有需要的話很樂意跟進，

you can absolutely there because one into the question about what we're doing to them enhanced enrollment and I'll just speak quickly about that, that we are putting a lot of effort to that meeting with investigators and each country and thought leaders, especially on a one to one level with Geron, Garen operations and clinical development staff as well as frequent virtual meetings and virtual. I guess you can call them like investigator type meetings to remind investigators about the study and to hear any feedback on enrollment. We also on with our medical affairs team have been engaging more aggressively with myelofibrosis advocacy groups, both in the US and international.

你絕對可以在那裡，因為有人問我們正在對他們做什麼，以提高入學率，我會很快談到這一點，我們正在為與調查人員、每個國家和思想領袖的會議付出很大的努力，特別是與 Geron、Garen 營運和臨床開發人員進行一對一的交流，以及頻繁的虛擬會議和虛擬會議。我想你可以將它們稱為調查員類型的會議，以提醒調查員有關該研究的資訊並聽取有關註冊的任何反饋。我們的醫療事務團隊也更積極地與美國和國際上的骨髓纖維化倡議團體合作。

Thanks, guys.

多謝你們。

Your next question comes from the line of Joel Beatty of Baird. Your line is open and thanks for taking the questions.

您的下一個問題來自貝爾德 (Baird) 的喬爾·比蒂 (Joel Beatty)。您的熱線已接通，感謝您提出問題。

The first one is what percent of luspatercept uses currently in RS positive compared to RS negative? And would you expect a similar split for imetelstat?

第一個是與 RS 陰性相比，目前 RS 陽性患者使用 luspatercept 的百分比是多少？您預計 imetelstat 也會有類似的分割嗎？

Yes, sure.

是的，當然。

So we don't have syndicated data to answer this question. What we do have is public statements from the companies stating that Anadys positive. They are very well penetrated and the numbers quoted are in excess of 65% from public statements from Squibb for RS positive. Does that answer your question?

所以我們沒有聯合數據來回答這個問題。我們所掌握的是各公司的公開聲明，顯示 Anadys 的態度是正面的。他們的滲透率非常高，引用的數字超過了施貴寶公開聲明中 RS 陽性的 65%。這是否回答你的問題？

Yes, that's helpful. Thank you. And then on the last question, is there a kind of specific definition of ESA failure and that might prompt starting imetelstat now? Or is there some clinical judgment involved? So I wonder if patients go through a period of time and with serially partially responding to ESAs

是的，這很有幫助。謝謝。然後關於最後一個問題，是否有一種 ESA 故障的具體定義，並且可能會提示現在啟動 imetelstat？或是否涉及一些臨床判斷？所以我想知道患者是否經歷過一段時間並且對 ESA 有連續部分反應

I asked Altix after the clinical trial, we had a specific definition and what will be on the label remains to be seen, but will be according to the investigator our sorry, physician adjustments.

臨床試驗後我問 Altix，我們有一個具體的定義，標籤上的內容還有待觀察，但我們會根據研究者的情況進行調整，抱歉，醫生。

I think if you have any further comments, sorry, go ahead.

我想如果您還有任何進一步的意見，抱歉，請繼續。

And yesterday and Joel, I also will point you to our deck that we are using for the call because we have recently completed on a survey of US physicians, 50 of them, both academic and community. And if you look on our debt expectations for imetelstat, we see ourselves being extremely well positioned across all the patient segments that we serve, in particular, what is highlighted from physicians and very favorably received by them. Our for imetelstat is the population which is ESA ineligible in the frontline setting and patients who are RS negative patients irrespective of either prior treatment with luspatercept or ESAs. And I think these are the places where we are extremely differentiated and are serving a very high level of unmet need.

昨天，喬爾，我還將向您介紹我們用於電話會議的平台，因為我們最近完成了一項針對美國醫生的調查，其中包括學術界和社區的 50 名醫生。如果你看看我們對 imetelstat 的債務預期，我們會發現我們在我們服務的所有患者群體中都處於非常有利的位置，特別是醫生強調並受到他們非常好評的部分。我們的 imetelstat 是在前線環境中不符合 ESA 資格的人群以及 RS 陰性患者，無論之前是否接受過 luspatercept 或 ESA 治療。我認為這些是我們極其與眾不同的地方，並且正在滿足非常高水平的未滿足需求。

Your next question comes from the line of Kalpesh Patel of B. Riley Securities. Your line is open.

您的下一個問題來自 B. Riley Securities 的 Kalpesh Patel。您的線路已開通。

Yes, hey, good morning. And thanks for taking the question. And I think Chip, you've previously said that you'd make the patent life cycle decision for applying the PTE. to the method of use patent around the time of FDA approval. So the question is, is that guidance unchanged today? Or does the delay in the MS trial readout sort of impact the thinking behind the patent strategy.

是的，嘿，早安。感謝您提出問題。我想 Chip，您之前說過您會為申請 PTE 做出專利生命週期決定。 FDA 批准前後的使用方法專利。那麼問題是，今天的指導方針是否不變？或者 MS 試驗結果的延遲會影響專利策略背後的想法？

Great question. Thanks, Kyle. But I think the the specifics of how application for PTE. works is a little bit above my pay grade, but I'll give you my understanding of it today as best I can on after you have your first approval, you can consider whether you have had a clear strategic idea of where you would like to apply PPD. And right now, all of that is pointing towards the method-of-use patents. The reason for that is fairly straightforward as many people in the investment community have pointed out many and you have pointed out in your coverage and we're covered quite well with the with the orphan drug exclusivity and you can apply in PTE. to the compact and wouldn't really trumps that. And so there's every reason to imagine putting the PTD. onto the MOU. We've done a lot of consideration and working on this and at the end of the day, we have to indicate to FDA when you plan at some point after approval, what we wanted to do and they will go and provide us with estimates of the exact time frames and so forth, there's kind of a process there, assuming all assuming all goes well, they're out. I think it's important to say that the X, we believe from our analysis of this in our outside terms analysis of this, that exclusivity would be extended to 2037, and it would very importantly for a method-of-use patent would apply. The PTE. would apply to all uses covered by the patent, including both MDS and AML. So a lot of incentives to to apply it to the methods of use claim, and we'll take that up. Obviously, the implications come much later. But I don't know of any reason that we should not indicate that that's our our current expectation.

很好的問題。謝謝，凱爾。但我覺得具體如何申請PTE。工作有點高於我的薪資等級，但今天我會盡我所能地向您提供我的理解，在您第一次批准後，您可以考慮是否對您想要的地方有一個清晰的戰略構想應用PPD。現在，所有這些都指向使用方法專利。原因相當簡單，正如投資界的許多人已經指出的那樣，您在報道中也指出了，我們在孤兒藥獨佔權方面得到了很好的保護，您可以在 PTE 中申請。到緊湊型並不會真正勝過這一點。因此，我們有充分的理由想像放置 PTD。到諒解備忘錄上。我們已經做了很多考慮並致力於此，最終，我們必須向 FDA 表明當您在批准後的某個時刻計劃時，我們想要做什麼，他們會向我們提供估計確切的時間框架等等，那裡有一個過程，假設一切順利，他們就出局了。我認為重要的是說，X，我們相信，從我們對外部條件的分析來看，排他性將延長至 2037 年，並且對於使用方法專利的申請來說，這將是非常重要的。PTE。將適用於該專利涵蓋的所有用途，包括 MDS 和 AML。因此，有許多動機將其應用到使用方法聲明中，我們將予以採納。顯然，其影響要晚得多。但我不知道有什麼理由我們不應該表明這是我們目前的期望。

Okay. Thank you. And we've been getting questions on the manufacturing and CMC front given what's happening in the industry. I guess if you can comment on the inspections and everything on that front. Okay. And then I have a follow-up.

好的。謝謝。鑑於該行業正在發生的情況，我們一直收到有關製造和 CMC 方面的問題。我想您是否可以對檢查以及這方面的所有內容發表評論。好的。然後我有一個後續行動。

Yes, I I think we're not going to provide specific numbers. I'll follow up there, but I think that we are comfortable and as things have proceeded to date, where still looking forward to, I could do for a date with an approval. And that's the best I can really say. We all know there. There's always some degree of uncertainty. But other than that, I don't think we're making specific comments about the piece by piece of march towards could do for you on any of the different fronts, including manufacturing inspections.

是的，我認為我們不會提供具體數字。我會跟進那裡，但我認為我們很舒服，而且隨著事情的進展，到目前為止，我仍然期待著，我可以在獲得批准的情況下進行約會。這是我能說的最好的話。我們都知道那裡。總是存在某種程度的不確定性。但除此之外，我認為我們不會就任何不同方面（包括製造檢查）的逐步進展對您做出的具體評論。

Okay. Okay. And then last one, we've been getting questions on we should be modeling the US launch and the initial ramp. I guess maybe one for Aneel. Are there good examples or analogs that the investor community can use to kind of project this at least for the initial ramp for the 1st year or two and regular Zelle was obviously approved a few years ago, but that market wasn't built at that time. So people are curious how they should model this now?

好的。好的。最後一個，我們一直收到關於我們應該對美國的發布和初始升級進行建模的問題。我想也許是給阿尼爾的。是否有很好的例子或類比，投資者社區可以用來至少在第一年或第二年的初始階段進行項目，常規 Zelle 顯然在幾年前就已獲得批准，但當時市場尚未建立。所以人們很好奇現在應該如何建模？

Yes. So on, I think the best guidance I would give is to focus on unmet need of this patient population. What we have heard very clearly in the low-risk MDS market, there is dissatisfaction predominantly along three segments. One is the need for better more effective products for patients who are high transfusion burden, which remain 40% and 50% of this marketplace or options for RS negative patients who today do not have effective therapies and patients, obviously who are ineligible for ESAs because their outcomes are pretty dismal. So our expectation is that on those are three patient populations where physicians will use a drug such as ours. We also know that as you yourself said, luspatercept has been in this marketplace for the last two to three years we would expect to see patients who have been treated with luspatercept and physicians are looking for more options are both our Phase two study and our Phase three part of the study covered the luspatercept pretreated patients. And given our uniqueness of our mechanism, we would expect to be effective in that population as well. So I think it's a mix of these patients. It's hard to point to one effective and alone because there are many characteristics which make each and every one of these launches unique. But I do think the unmet need is very high. Our data remains highly differentiated and the dissatisfaction and the need for new treatments, we should see imetelstat well positioned and we adopted within the armamentarium of the physicians as they treat their risk MDS patients.

是的。因此，我認為我給出的最佳指導是關注該患者群體未滿足的需求。我們在低風險 MDS 市場中非常清楚地聽到，主要在三個細分市場上存在不滿。一是需要為高輸血負擔的患者提供更好、更有效的產品，這些患者仍佔該市場的40% 和50%，或為目前沒有有效療法的RS 陰性患者和顯然不符合ESA 資格的患者提供選擇，因為他們的結果非常慘淡。因此，我們的期望是，醫生將在這三個患者群體中使用像我們這樣的藥物。我們也知道，正如您自己所說，luspatercept 在過去的兩到三年裡一直在這個市場上，我們希望看到接受過luspatercept 治療的患者，醫生正在尋找更多的選擇，無論是我們的二期研究也是我們的二期研究研究的三部分涵蓋了luspatercept預處理的病人。鑑於我們機制的獨特性，我們希望在該人群中也能發揮作用。所以我認為這是這些患者的混合體。很難指出哪一款產品是有效且單獨的，因為有許多特徵使得每個產品都獨一無二。但我確實認為未滿足的需求非常高。我們的數據仍然高度分化，並且對新治療方法的不滿和需求，我們應該看到 imetelstat 處於有利位置，並且我們在醫生治療高風險 MDS 患者時在他們的醫療設備中採用了 imetelstat。

Okay. Thank you very much for taking the questions.

好的。非常感謝您接受提問。

Thanks, Kelvin.

謝謝，凱爾文。

That concludes our Q&A session. I will now turn the conference back over to Aron Feingold for closing remarks.

我們的問答環節到此結束。現在，我將把會議轉回阿倫法因戈爾德 (Aron Feingold) 致閉幕詞。

Thanks so much to everyone 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.

非常感謝大家今天加入我們。我們感謝您對 Geron 的關注，並期待在這個激動人心的時刻為您提供最新資訊。對我們公司來說。

However, that when everyone This concludes today's conference call, you may now disconnect.

但是，當大家結束今天的電話會議時，您現在可以斷開連線。