Geron Corp (GERN) 2023 Q4 法說會逐字稿

My name is Rob and I will be your conference operator today. At this time, I would like to welcome everyone to the Geron Corporation's Fourth Quarter and Full Year 2023 conference call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. If you'd 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 again, press the star one. Thank you, Aaron Feingold, Vice President of Investor Relations and Corporate Communications. You may begin your conference.

我叫羅布，今天我將擔任你們的會議操作員。此刻，我歡迎大家參加 Geron 公司 2023 年第四季和全年電話會議。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問，只需按星號，然後按電話鍵盤上的數字 1 即可。如果您想再次撤回您的問題，請按星號。謝謝投資人關係和企業傳播副總裁 Aaron Feingold。您可以開始您的會議了。

Good morning, everyone. Welcome to the Geron Corporation Fourth Quarter and Full Year 2023 earnings conference call. I am Aaron fine gold Chair and Vice President of Investor Relations and Corporate Communications. And I'm joined today by several members of Darren's management team, Dr. John Scarlett, Chairman and Chief Executive Officer, Michelle Robertson, Executive Vice President and Chief Financial Officer, Dr. Fowler, Executive Vice President and Chief Medical Officer, and Neil Cooper, Executive Vice President of Corporate Strategy and Chief Commercial Officer, and Dr. Andrew grassland, Executive Vice President and Chief Operating Officer.

大家，早安。歡迎參加 Geron Corporation 2023 年第四季和全年財報電話會議。我是 Aaron Fine Gold 主席兼投資者關係和企業傳播副總裁。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、執行副總裁兼財務長米歇爾·羅伯遜、執行副總裁兼首席醫療官福勒博士以及尼爾庫珀，公司策略執行副總裁兼首席商務官，安德魯·格拉斯蘭博士，執行副總裁兼首席營運官。

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 any of that 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 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 and undertakes no duty or obligation to update our forward-looking statements.

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任何預期臨床和商業事件及相關時間表的監管批准、Geron 財務資源的充足性和其他非歷史事實的陳述。實際事件或結果可能有重大差異。因此，我建議您參閱Geron 向SEC 提交的最新定期報告中「風險因素」標題下的討論，該討論指出了可能導致實際結果與前瞻性陳述中包含的結果存在重大差異的重要因素，並且不承擔任何責任或義務。更新我們的前瞻性陳述的義務。

And with that, I'll turn the call over to Tim.

然後，我會將電話轉給提姆。

Yes.

是的。

Thanks, Aaron. Good morning, everyone. Thanks for joining us today. Cyren's progress and execution throughout 2023 has paved the way for a potentially transformational 2024 as we plan for the transition to becoming a commercial company, FDA's assigned a PDUFA date of June 16th, 2024 for imetelstat for the treatment of transfusion-dependent anemia in patients with lower risk MDS and has also provided notice that is scheduled and Kodak as part of the imetelstat NDA review to be held on March 14th, 2024. In addition, a review of our NDA for the same indication is expected to be completed in early 2025. We're focused on and preparing for these critical next steps in the regulatory review process, which we hope will result in approval of what we believe is a highly differentiated an important treatment option for patients with transfusion dependent lower risk MDS. The publications from our pivotal IMerge Phase three clinical trial, including most recently in The Lancet, still robust response rate and an unprecedented durability of red blood cell transfusion independence with imetelstat treatment across multiple MDS patient subgroups, addressing areas of high unmet need. Additional unique attributes of imetelstat include patient reported outcomes of less fatigue and significant reductions in variant allele frequency and commonly mutated MDS gene with a well-characterized safety profile of generally manageable and short-lived, thrombocytopenia and neutropenia, we believe the clinical evidence supporting the benefits of imetelstat is compelling, and then it can become a transformational treatment option for currently underserved populations if approved by regulatory authorities behind our lead indication low-risk MDS is a similarly important program, the Phase three IMPACT MF clinical trial and Jackie relapse and refractory myelofibrosis. An interim analysis is expected for this study in the first half of 2021 impact. Mf is the first and only MS Phase three trial with overall survival as a primary endpoint. If the expected interim analysis in 2025 or the final analysis expected in 2026 is positive. These data could be transformational for patients with Jack, I relapse and refractory MF live dismal survival prognosis today, our two lead indications for imetelstat represent significant commercial opportunities with a total addressable market or TAM of $3.5 billion for each indication across the U.S. and EU in 2031 thus representing a combined $7 billion TAM for transfusion dependent lower risk MDS and relapse refractory. Given this very substantial opportunity, unmet and deep unmet need and transfusion dependent low risk MDS, we expect to be prepared to launch and self commercialize imetelstat in its lead indication upon potential FDA approval in the middle of this year. We have also completed multiple long-lead activities to prepare Geron imetelstat and the market for our potential launch in the EU with the goal of ensuring broad access and reimbursement for our important medicines. Moreover, if Imetelstat is approved by the European Commission in transfusion-dependent, lower-risk MDS. We expect 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 be able to provide an update later this year.

謝謝，亞倫。大家，早安。感謝您今天加入我們。Cyren 在2023 年的進展和執行為潛在的轉型2024 年鋪平了道路，因為我們計劃轉型成為一家商業公司，FDA 為imetelstat 指定的PDUFA 日期為2024 年6 月16 日，用於治療患有輸血依賴性貧血的患者風險較低的 MDS，並且還提供了預定通知，柯達作為 imetelstat NDA 審查的一部分將於 2024 年 3 月 14 日舉行。此外，我們針對同一適應症的 NDA 審查預計將於 2025 年初完成。我們正在專注於並為監管審查過程中的這些關鍵的後續步驟做好準備，我們希望這些步驟將導致批准我們認為對於輸血依賴性低風險 MDS 患者而言高度差異化的重要治療選擇。我們關鍵的IMerge 三期臨床試驗的出版物（包括最近發表在《柳葉刀》上的出版物）在多個MDS 患者亞組中使用imetelstat 治療的反應率仍然強勁，並且紅血球輸注獨立性空前持久，解決了高度未滿足需求的領域。imetelstat 的其他獨特屬性包括患者報告的疲勞減輕、變異等位基因頻率和常見突變MDS 基因顯著降低的結果，以及通常可控制和短暫的、血小板減少症和中性粒細胞減少症的良好特徵安全性，我們相信臨床證據支持imetelstat 的好處是引人注目的，如果我們的主要適應症低風險MDS 背後的監管機構批准，它可以成為目前服務不足的人群的一種變革性治療選擇。低風險MDS 是一個同樣重要的計劃，第三期IMPACT MF 臨床試驗和Jackie 復發和難治性骨髓纖維化。預計研究將在 2021 年上半年進行中期分析。Mf 是第一個也是唯一以總存活期為主要終點的 MS 三期試驗。如果預計2025年的中期分析或預計2026年的最終分析是正面的。這些數據對於Jack、I 復發和難治性MF 患者的生存預後可能具有變革意義，我們的imetelstat 的兩個主要適應症代表了巨大的商業機會，在美國和歐盟，每個適應症的總可尋址市場或TAM 為35 億美元。因此，到 2031 年，用於治療輸血依賴性低風險 MDS 和復發難治性 MDS 的 TAM 總額將達到 70 億美元。鑑於這一非常重要的機會、未滿足和深度未滿足的需求以及輸血依賴性低風險 MDS，我們預計在今年年中 FDA 可能批准其主要適應症後，準備推出並自我商業化 imetelstat。我們也完成了多項長期活動，為 Geron imetelstat 和我們可能在歐盟推出的市場做好準備，目標是確保我們重要藥物的廣泛獲取和報銷。此外，如果 Imetelstat 獲得歐盟委員會批准用於輸血依賴性、低風險 MDS。我們預計將於 2025 年在歐洲進行商業發布。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。

Lastly, we ended 2023 with a strong cash position of approximately $378 million, which based on our current plans and expected available resources we expect will enable us to fund a potential successful launch in transfusion dependent lower-risk MDS in the U.S. and fund our planned operations into the third quarter of 2025. We believe our differentiated product candidates, the very important commercial opportunities in transfusion dependent, lower risk, MDS and relapse refractory MS sales excellence and experience to our employees and the financial resources to execute on our near term milestones puts us in a strong position for value creation.

最後，到2023 年年底，我們擁有約3.78 億美元的強勁現金頭寸，根據我們目前的計劃和預期可用資源，我們預計這將使我們能夠為在美國成功推出輸血依賴性低風險MDS 提供資金，並為我們計劃的項目提供資金運作至 2025 年第三季。我們相信，我們的差異化候選產品、輸血依賴性、低風險、骨髓增生異常綜合徵和復發難治性多發性硬化症方面的非常重要的商業機會、我們員工的卓越銷售和經驗以及執行近期里程碑的財務資源，使我們在價值方面處於有利地位創建。

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

這樣，我會將電話轉給費伊，以了解監管和臨床更新日的情況。

Thanks, Tim, and good morning to everyone on the call. As Chip mentioned, we are deeply focused on the regulatory processes for our imetelstat NDA and MAA, which are currently under review by the FDA and EMA for the treatment of transfusion-dependent anemia in patients with lower-risk MDS who have failed to respond or have lost response to or are ineligible for ESAs.

謝謝提姆，祝所有參加電話會議的人早安。正如 Chip 所提到的，我們非常關注 imetelstat NDA 和 MAA 的監管程序，目前 FDA 和 EMA 正在審查這些程序，用於治療低風險 MDS 患者的輸血依賴性貧血，但這些患者未能做出反應或已失去對ESA 的回應或不符合ESA 資格。

As previously disclosed, the FDA assigned a PDUFA action date of June 16th, 2024 on January 30th, 2024. The FDA also provided notice in the Federal Register that it had scheduled an ODAC. as part of the imetelstat NDA review to be held virtually on March 14th, 2024. We feel very well-prepared for the scheduled Kodak. We've been working for many months with an expert consultancy group, which complements our deep in-house regulatory experience. I am personally excited to have the opportunity to discuss imetelstat with experts and peers, and we believe imetelstat could be an important and compelling new medicine for transfusion dependent low risk MDS patients. Our readout of positive top line results from our pivotal IMerge trial in January 2023 was followed last year by a number of additional presentations and analyses of the data, including at Asco and Ihab earlier in the year and last quarter at ASH, this growing body of data from the trial continue to give us confidence in what we believe is a meaningful clinical benefit and manageable safety profile with imetelstat in patients with transfusion dependent lower risk MDS. As reported at these conferences, the clinical attributes of imetelstat were differentiated, particularly with respect to high RBCTI. response rate, durability of response and the consistency of effect across MDS subgroups that have historically been very difficult to treat the Lancet published results from our IMerge Phase three trial this past December, a strong validation of the importance of the study within the field as well as a powerful way to reach rheumatologists and other providers globally with these potentially practice-changing results that offer the possibility of relief for lower risk MDS patients from chronic Reliance and blood cell transfusions.

如先前揭露的，FDA 將 PDUFA 行動日期指定為 2024 年 1 月 30 日，即 2024 年 6 月 16 日。FDA 也在《聯邦公報》中發出通知，稱其已安排 ODAC。作為將於 2024 年 3 月 14 日虛擬舉行的 imetelstat NDA 審查的一部分。我們感覺已經為預定的柯達做好了充分的準備。我們已經與專家諮詢小組合作了好幾個月，這補充了我們深厚的內部監管經驗。我個人很高興有機會與專家和同行討論 imetelstat，我們相信 imetelstat 可能成為輸血依賴性低風險 MDS 患者的一種重要且引人注目的新藥物。我們在2023 年1 月公佈了關鍵IMerge 試驗的積極頂線結果，隨後在去年進行了許多額外的數據演示和分析，包括今年早些時候在Asco 和Ihab 以及上個季度在ASH 上進行的數據演示和分析，ASH 是一個不斷壯大的機構該試驗的數據繼續讓我們相信，伊美司他對於輸血依賴性低風險 MDS 患者俱有有意義的臨床益處和可控的安全性。正如這些會議上所報告的，imetelstat 的臨床屬性有所不同，特別是在高 RBCTI 方面。歷史上很難治療的 MDS 亞組的緩解率、緩解持久性和效果的一致性 《刺胳針》去年 12 月發布了我們的 IMerge 三期試驗的結果，有力地驗證了該領域研究的重要性作為向全球風濕病學家和其他提供者提供這些可能改變實踐的結果的有力方式，這些結果為低風險MDS 患者提供了緩解長期Reliance 和血球輸注的可能性。

Turning now to our Phase three trial of imetelstat in relapsed refractory MF. We were excited to have completed 50% enrollment in the study in November of 2023. We continue to expect an interim analysis in the first half of 2025, which will occur when approximately 35% of the planned enrolled patients have died. A final analysis is expected in the first half of 2026 when over 50% of the planned enrolled patients have died. We look forward to continuing to keep you updated on this important study.

現在轉向我們的 imetelstat 治療復發難治性 MF 的第三階段試驗。我們很高興在 2023 年 11 月完成了該研究 50% 的入組率。我們繼續預計在 2025 年上半年進行中期分析，屆時計劃入組的患者中約有 35% 已經死亡。最終分析預計將在 2026 年上半年進行，屆時計劃入組患者的死亡人數將超過 50%。我們期待繼續向您通報這項重要研究的最新情況。

Lastly, we are also evaluating imetelstat in a Phase one study as a combination therapy with ruxolitinib in patients with Frontline myelofibrosis. Our main goal for the combination study, known as improvement as to determine the safety profile of the combination regimen of ruxolitinib and imetelstat, as well as to explore the potential activity in a frontline MF disease setting.

最後，我們也在一項第一階段研究中評估 imetelstat 作為與魯索替尼聯合療法治療第一線骨髓纖維化患者的情況。我們聯合研究的主要目標是確定魯索替尼和伊美司他聯合方案的安全性，並探索在一線 MF 疾病中的潛在活性。

In January 2024, we escalated to the third of four dose cohorts in the study following a unanimous decision by the study's safety evaluation team or SEC, who reviewed the second cohort data, we are very pleased with the progress and look forward to providing future updates.

2024 年1 月，根據研究的安全評估小組或SEC 審查了第二組數據的一致決定，我們升級到研究中四個劑量組中的第三個，我們對進展感到非常滿意，並期待提供未來的更新。

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

這樣，我會將電話轉給阿尼爾以獲取商業更新。阿尼爾？

Thank you, fair, and good morning, everyone. I look forward to discussing first, where we see significant unmet need in the market, and then we'll provide a brief update on our US launch plans. There remains significant unmet need across key transfusion dependent lower risk MDS patient populations that are underserved by current available treatment options. Approximately 10% of lower risk MDS patients are not eligible for ESAs and represent a very high unmet need subgroup. Rs negative patients make up approximately 75% of lower-risk MDS patients and RA population, particularly vulnerable to poor clinical outcomes. There are no therapies indicated for the treatment of anemia in RS negative patients once they are relapsed or refractory to ESAs. Rs positive patients make up approximately 25% of the lower risk MDS patients and most who are high transfusion burden, lack effective treatment options. These underserved subgroups are at a greater risk for disease progression and suboptimal survival and are in the need for more effective treatment options.

謝謝大家，公平，大家早安。我期待首先討論我們看到市場上未滿足的重大需求，然後我們將提供有關我們在美國推出計劃的簡要更新。目前可用的治療方案未能充分滿足關鍵的輸血依賴性低風險 MDS 患者群體的需求，但仍存在大量未滿足的需求。大約 10% 的低風險 MDS 患者不符合 ESA 資格，是一個非常高的未滿足需求亞組。Rs 陰性患者約佔低風險 MDS 患者和 RA 族群的 75%，特別容易出現不良臨床結果。對於復發或對 ESA 無效的 RS 陰性患者，沒有任何治療方法可以治療貧血。Rs 陽性患者約佔低風險 MDS 患者的 25%，大多數輸血負擔較高，缺乏有效的治療選擇。這些服務不足的亞組疾病進展和生存不佳的風險更大，需要更有效的治療方案。

Moving on to an update on U.S. launch preparations without the due for date, just about 3.5 months away, we have completed multiple critical launch readiness activities and plan to be ready to launch imetelstat in the US market upon potential approval, long lead time activities, such as securing our global trademark on our brand name, manufacturing of commercial supply are now complete in preparation of launch. We have also finalized our distribution network and our patient support providers. In addition, we have onboarded and fully integrated a highly experienced commercial and medical affairs team into general. We continue to transition Geron towards a commercial company with the integration and adoption of systems and processes. We recognize and record revenues and the continued refinement of engagement plans with marketing, commercial access, payer and reimbursement stakeholders.

接下來是關於美國上市準備工作的最新情況，距離截止日期僅剩大約3.5 個月，我們已經完成了多項關鍵的上市準備活動，併計劃在可能獲得批准後準備在美國市場推出imetelstat，準備時間較長的活動，例如，在我們的品牌名稱上確保我們的全球商標，商業供應的製造現已完成，準備推出。我們也最終確定了我們的分銷網絡和患者支援提供者。此外，我們還聘請並全面整合了一支經驗豐富的商業和醫療事務團隊。我們繼續透過系統和流程的整合和採用，將 Geron 轉型為商業公司。我們確認並記錄收入以及與行銷、商業准入、付款人和報銷利害關係人的參與計劃的持續改進。

With regard to our field team, all regional business directors were onboarded in early January and key account manager roles are being recruited. We expect to onboard the sales force in the first and second quarter of 2024. I'm very excited by the caliber of talent we have recruited onto the commercial team and across the organization. Our cross-functional launch team have deep oncology expertise and operational experiences, and they have been part of multiple oncology launches. We are excited about the opportunity to bring this innovative therapy to patients and are confident in our readiness to launch imetelstat in the US market upon potential FDA approval.

至於我們的現場團隊，所有區域業務總監均已於一月初入職，並且正在招募關鍵客戶經理職位。我們預計將在 2024 年第一季和第二季組成銷售團隊。我對我們在商業團隊和整個組織中招募的優秀人才感到非常興奮。我們的跨職能發布團隊擁有深厚的腫瘤學專業知識和營運經驗，並且他們參與了多項腫瘤學發表。我們很高興有機會將這種創新療法帶給患者，並對我們準備好在 FDA 批准後在美國市場推出 imetelstat 充滿信心。

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

現在，我將把電話轉給米歇爾，以了解最新的財務狀況。

Michelle?

米歇爾？

Thanks, Neil, and good morning, everyone for joining our Q4 and full year 2023 financials. Please refer to the press release we issued this morning, which is available on our website.

謝謝 Neil，大家早安，關注我們的第四季和 2023 年全年財務報告。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。

I will now review some highlights from the quarter and full year. At the end of 2023, our cash, cash equivalents and marketable securities were $378.1 million, approximately $2.5 million warrants outstanding and the potential proceeds from the warrants of $3.2 million total operating expenses for the three and 12 months ended December 31st, 2023, or $54.3 million and $194.1 million, respectively, compared to $42 million and $139.1 million for the comparable 2022 period. R&D expenses for the three and 12 months ended December 31st, 2023 was $32.9 and $125 million, respectively, compared to $28.2 million and $95.5 million for the same period in 2022. Expenses have increased year over year, primarily related to supporting our Phase three clinical trials by merge and impact MF, both personnel and consulting costs increased to support regulatory submissions and increased investment in manufacturing as we prepare for the potential U.S. commercialization of imetelstat in transfusion dependent lower risk MDS G&A expenses were $21.4 million and $69.1 million for the three and 12 months ended December 31st, 2023, compared to $13.8 million and $43.6 million for the same periods in 2022. The increase in G&A expense is primarily attributed to headcount and external expenses to support the commercial readiness activities. At the end of December 31st, 2023, the company had 141 employees, which we project will grow to approximately 270 employees by the end of 2024, subject to receiving FDA approval of imetelstat. The increase in headcount is primarily in the commercial and medical affairs teams. Our projected full year 2024. Operating expenses are expected to be between $270 million and $280 million based on our current operating cadence and expectations regarding the timing of a potential approval of our imetelstat NDA that is currently under FDA review and subsequent potential U.S. commercial launch. We believe that our current cash resources, together with projected revenues from US sales of imetelstat proceeds from the exercise of outstanding warrants and funding under our loan facility will be sufficient to support our operations into the third quarter of 2025.

我現在將回顧本季和全年的一些亮點。截至2023 年底，我們的現金、現金等價物及有價證券為3.781 億美元，未償還認股權證約為250 萬美元，認股權證的潛在收益為320 萬美元，截至2023 年12 月31 日的三個月和12 個月的總營運費用為54.3 美元分別為 100 萬美元和 1.941 億美元，而 2022 年同期為 4,200 萬美元和 1.391 億美元。截至2023年12月31日的三個月和十二個月的研發費用分別為32.9美元和1.25億美元，而2022年同期為2820萬美元和9550萬美元。費用逐年增加，主要與透過合併和影響MF 支持我們的第三期臨床試驗有關，人員和諮詢成本增加以支持監管提交，並增加對製造的投資，因為我們為imetelstat 在輸血依賴性藥物在美國的潛在商業化做準備截至2023 年12 月31 日的三個月和12 個月，風險較低的MDS 一般管理費用分別為2,140 萬美元和6,910 萬美元，而2022 年同期為1,380 萬美元和4,360 萬美元。一般及行政費用的增加主要歸因於員工人數和支持商業準備活動的外部費用。截至 2023 年 12 月 31 日，該公司擁有 141 名員工，我們預計到 2024 年底，該員工人數將增加到約 270 名，前提是 imetelstat 獲得 FDA 批准。人員數量的增加主要是商務和醫療事務團隊。我們預計 2024 年全年。根據我們目前的營運節奏以及目前正在接受 FDA 審查的 imetelstat NDA 的潛在批准時間以及隨後可能在美國商業推出的預期，營運費用預計在 2.7 億美元至 2.8 億美元之間。我們相信，我們目前的現金資源，加上在美國銷售 imetelstat 的預計收入（透過行使未償認股權證所得收益）以及我們貸款安排下的資金，將足以支持我們到 2025 年第三季的營運。

I will now turn the call back over to Tim.

我現在將把電話轉回給蒂姆。

Yes.

是的。

Thanks, Michelle, for Geron. Our progress in 2023 represented the culmination of a many year multifaceted scientific and drug development journey, the goal of which is to translate the promise of Swan Lake in addition into a potentially powerful medicine today, we're just 3.5 months away from the producer date for our first-in-class telomerase inhibitor, which we believe has the potential to offer important and potentially life-changing treatment options to patients with transfusion-dependent lower-risk MDS. We believe this is a robust commercial opportunity, and we're on track for a successful transition to becoming a commercial company. In addition, we're excited by the momentum in our Phase three IMPACT MS trial, which is 50% enrolled as of November 2023, and for which we expect an interim analysis in the first half of 2025. We believe these programs carry significant value for patients and shareholders alike, and we look forward to keeping you updated on our progress, and we'll now open the line to questions.

謝謝米歇爾，謝謝傑隆。我們在 2023 年取得的進展代表了多年多方面科學和藥物開發之旅的頂峰，其目標是將天鵝湖的承諾轉化為今天潛在的強效藥物，距離生產日期僅 3.5 個月我們的一流端粒酵素抑制劑，我們相信它有潛力為輸血依賴性低風險MDS 患者提供重要且可能改變生活的治療選擇。我們相信這是一個巨大的商業機會，我們正在成功轉型為商業公司。此外，我們對第三階段 IMPACT MS 試驗的動能感到興奮，截至 2023 年 11 月，該試驗的入組率為 50%，我們預計將在 2025 年上半年進行中期分析。我們相信這些計劃對患者和股東都具有重大價值，我們期待向您通報我們的最新進展，我們現在將開放提問。

Operator, at this time, I would like to remind everyone in order to ask a question, press star then the number one on your telephone keypad. Your first question comes from the line of Corinne Jenkins from Goldman Sachs.

接線生，此時我想提醒大家，要提問，請按星號，然後按電話鍵盤上的數字 1。你的第一個問題來自高盛的 Corinne Jenkins。

Your line is open in mining, maybe maybe one from us and a follow-up to that. How would you characterize the likelihood that you could see imetelstat approved with either a black-box warning and or a REMS program? And then more importantly, what do you view as the implications from a commercial perspective under either scenario?

您的採礦線路已開放，也許是我們的一條線路以及後續線路。您如何描述 imetelstat 透過黑盒警告和/或 REMS 計劃獲得批准的可能性？更重要的是，您認為這兩種情況下從商業角度來看會產生什麼影響？

Well, a lot of competition, so let me say first of all and we're going to do that offline over everybody.

嗯，競爭很多，所以首先我要說的是，我們將在線下對每個人進行競爭。

Well. So I'll just say one, so nothing to comment on ongoing conversations with regulators on the for the opportunities that we're very, very close to our leasing office with them.

出色地。所以我只想說一件事，所以對與監管機構正在進行的對話沒有什麼可評論的，因為我們與他們的租賃辦公室非常非常接近。

And let me just say I don't think it's one thing.

我只想說我不認為這是一回事。

I don't think that from our perspective, either black box warning from the Navy are really struggling. It's warranted to BP. How all of that [1 billion] is a little niche segment for us that we feel is still very strong because of the new site and its ability to we used safely and effectively our cell sites private population.

我認為從我們的角度來看，海軍的黑盒子警告並沒有真正陷入困境。這是向 BP 保證的。所有這些 [10 億] 對我們來說都是一個小眾細分市場，我們認為它仍然非常強大，因為新站點及其我們安全有效地使用我們的蜂窩站點私人人口的能力。

Okay, thanks. Just one quick 1 to 7.1 question on the embedded commercial products commercial implications if it was to be implemented.

好的謝謝。只是一個簡單的 1 到 7.1 問題，涉及嵌入式商業產品的商業影響（如果要實施）。

So from current speculation, I think I'll stay out of that cycle. So we I think everybody understands well. It all depends, and it certainly when it comes to either black boxes or volumes, a contraindication fees at all, feel on other things that are nuanced machines are drawn out reform from separation funds. It's never done probably from our process completely done on the bottom, the guidance, but that's not where we're focused forward on beyond those types of physicians, we hope I think.

因此，從目前的猜測來看，我認為我不會陷入這個循環。所以我想每個人都很好理解。這一切都取決於，當然，當涉及到黑盒子或卷時，完全有禁忌費，感覺其他細微差別的機器是從分離基金中抽出改革的。從我們的流程來看，這可能從未完成過，完全是在底層、指導上完成的，但我認為，我們希望除了這些類型的醫生之外，這不是我們關注的重點。

Okay.

好的。

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

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

Yes, hey, good morning and thanks for taking the question. And there was a letter submitted to the ODAC members by an independent group regarding the Empatic safety for imetelstat. And the conclusion on that letter was positive overall for imetelstat. But I guess the question is, have you requested any other independent assessments for maybe additional topics such as evaluating the safety of the cytopenias from all the studies before the AdCom?

是的，嘿，早上好，感謝您提出問題。一個獨立團體向 ODAC 成員提交了一封關於 imetelstat 的 Emmatic 安全性的信函。這封信的結論總體上對 imetelstat 是正面的。但我想問題是，您是否要求對可能的其他主題進行任何其他獨立評估，例如評估 AdCom 之前所有研究中血球減少症的安全性？

Well, I think we have a profile for those who are aren't aware of it of both of what model was some and finally, the numbers of our product. And since your IPO valuation permanently out of the support agency bought improvement, little ups. Votes were viewed on Bosch almost a decade ago. So very grow one or two. And if people do that soon, it looks for from drug-induced liver injury and thoughtful on pump. We are in stage one and two are overseeing all of the results of our drilling program on a study. They did a wonderful job. We had quarterly meetings that have looked at of the scrap of inflammation in the PC market and the way they look today, every scrap of inflammation that relates in any way, shape or form to to liver toxicity or liver safety on the level sort of outlook for people to me that simply reaffirms bill, but we just spoke about, of course, on the voice of blood through Liverpool software. So that's really where it came from. And I'll be honest, I never thought about it of that about. So kind of more a well compounds go earlier the interest from the people, our will hold a lot of interest, especially from them talking about.

好吧，我認為我們為那些不了解我們產品型號和產品數量的人提供了一份簡介。而且自從你的IPO估值永久脫離機構買入的支持改善後，漲幅不大。大約十年前，人們就對博世進行了投票。所以非常長一兩個。如果人們很快就這樣做，它會尋找藥物引起的肝損傷並考慮幫浦的情況。我們正處於第一階段和第二階段，正在監督鑽探計劃研究的所有結果。他們做得非常出色。我們召開季度會議，研究 PC 市場中的發炎碎片及其今天的樣子，以任何方式、形狀或形式與肝毒性或肝臟安全性相關的每一個發炎碎片，其前景水平對於我來說，這只是重申了法案，但我們只是談論了，當然，透過利物浦軟體的血液之聲。這就是它的真正來源。老實說，我從來沒有想過這個問題。因此，人們的興趣越早，我們就越感興趣，尤其是他們談論的。

Okay.

好的。

Thanks for taking the questions.

感謝您提出問題。

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

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

It just says yes, that you're taking the questions, I guess, Tim, and again, I'm not sure if you'll be able to speak to this, but can't can you remind us just what the frequency of platelet and cell count monitoring in the IMerge trial was? And I guess as you think about a potential product label, would you expect that monitoring requirement to be a bit more stringent than what it was in the trial?

它只是說是的，我想你正在回答這些問題，蒂姆，再說一次，我不確定你是否能夠回答這個問題，但是你能提醒我們一下問題的頻率嗎？ IMerge 試驗中的血小板和細胞計數監測是？我想當您考慮潛在的產品標籤時，您是否會期望監控要求比試驗中的要求更嚴格一些？

And I think if I recall, Steve, it was equally are monitoring several cycles on, I think whatever was in the trial, it's not unlikely. And to be looked at, by the way, the results are sort of a de facto standard. And I will comment on labor and decide where that will go exactly all, but I'll do what makes sense on that's given us the authority to withhold votes on the frequency on the sort of the course of the sale of the site of disease such as Zoom or indeed short-life and well-managed, knowledgeable on destination site. But our learning a lot because we were selling them a lot well. So I think that's what the tactics are limited in what I would expect going forward at all, Paul Bulmahn 32 subjects.

我想，如果我記得，史蒂夫，同樣正在監測幾個週期，我認為無論試驗中發生什麼，這都不是不可能的。順便說一下，結果是事實上的標準。我將對勞工發表評論並決定其具體去向，但我會做有意義的事情，這使我們有權對疾病網站的銷售過程的頻率保留投票，例如Zoom 確實壽命短、管理完善、對目的地網站了解豐富。但我們學到了很多東西，因為我們賣得很好。所以我認為這就是我所期望的策略在未來的局限性，Paul Bulmahn 32 主題。

Okay.

好的。

And you know, I guess what proportion of these patients? I mean, obviously, they're low-risk MDS and dysplastic marrow, but do you know what proportion of them are already doing weekly cell counts, whether it's at home, whether it's in a home office, what will it do to develop an interest cost from now on?

你知道，我猜這些患者佔多少比例？我的意思是，很明顯，他們是低風險骨髓增生異常綜合徵和發育不良骨髓，但你知道他們中有多少比例已經每週進行細胞計數嗎？無論是在家裡，還是在家庭辦公室，開發一種從現在起利息費用？

I would say that because it depends on what we're holding our own internally. And as you say, column where the what the level of the smaller displays and so on so forth and what their own extensive as you saw in the placebo arm we hold on, we will one person's all too, and simply also solid meaningful outside of renewals of all these amounts that were receiving placebo on whatever the Autobahn 14 and so on. So but a lot of money, I think from resolute on top of the regular monitoring probably assume associated with different on the Oakley products, 15 social space. So along with the associated total votes and proxies. So on my guess is that this would be something that would solve it are we certainly drawn most all to Paul just would follow very carefully. Just kind of a sense on what ultimately will be up to Brady, our position on whatever global sites off to the side of how the frequency and how that sort of plays out over the course of the patient's treatment with Olive Garden.

我之所以這麼說，是因為這取決於我們內在的立場。正如你所說，列中較小顯示的水平等等以及他們自己廣泛的內容，正如你在我們持有的安慰劑臂中看到的那樣，我們也將是一個人的全部，並且也簡單地在之外也具有堅實的意義更新所有在 14 號高速公路等上接受安慰劑的所有金額。所以，但是很多錢，我認為從定期監控的決心來看，可能會假設與不同的 Oakley 產品相關，15 個社交空間。以及相關的總票數和代理權。所以我的猜測是，這將是解決這個問題的方法，因為我們肯定最吸引保羅，只是會非常仔細地遵循。只是對布雷迪最終會做什麼有一種感覺，我們在全球任何網站上的立場都與頻率以及在患者接受橄欖園治療的過程中如何發揮作用有關。

And then maybe just to kind of a bigger picture question. I mean, there's obviously kind of this ongoing narrative amongst investors regarding the exclusivity runway and the development program for imetelstat here is still not necessarily expanding, but it's being broadened into some additional indications. And so just curious I guess, you know, it does do these Phase one studies reflect here in terms of confidence in the IPU. or do you think that these are opportunities you can bring online quickly, maybe carve out some additional orphan drug designations would just be kind of interested in terms of how you're thinking about the longer term R & D program for this drug store.

然後也許只是為了解決一個更大的問題。我的意思是，投資者之間顯然有一種關於獨家跑道的持續敘述，並且 imetelstat 的開發計劃仍然不一定擴大，但它正在擴大到一些額外的適應症。所以我只是好奇，你知道，這些第一階段研究確實反映了對議會聯盟的信心。或者您是否認為這些是您可以快速上線的機會，也許開闢一些額外的孤兒藥指定只是對您如何考慮該藥店的長期研發計劃感興趣。

So I think we've talked about it briefly just to be crystal clear to improve Omar and on on the AML study to book further restructuring on the backbone Yes, correct.

所以我認為我們已經簡單地討論過這個問題，只是為了清楚地改進奧馬爾，並在反洗錢研究上預定對骨幹網的進一步重組是的，正確的。

So the reps combo study and just some of the other thoughts phase, most of it will not stop search.

因此，代表組合研究和其他一些想法階段，大多數都不會停止搜尋。

So Ultrabook will come from Bobby on to public company development regardless of quality, where we put all the nuances of the license conditions, I think we see somebody in combinations in some different utilities and plugs and start putting on thinking about what type of opportunities we'll have to leave it on the high level on that topic.

因此，超極本將由Bobby 轉向上市公司開發，無論品質如何，我們都會考慮許可條件的所有細微差別，我認為我們會看到有人將一些不同的實用程式和插頭組合在一起，並開始思考我們會獲得哪些類型的機會我們必須將其留在該主題的高水準上。

We do, Bob, on the places that we think if we placed affiliates benefit to be derived. Our replacement parts will be dependent on one person, perhaps starting to roll out as a really good example, it's new What about to the consumer. We have a whole series of preclinical. So it's done on a number of years ago now one bond borrowing world got robbed of phone calls from banks. Look, the question of whether or not there were different ways to slice funded intrinsic activity. And that's one reason we've done some of the south that have transformed on ultimately of the funds flow, myelofibrosis. It throughput outcomes from what we've seen is that it's only about truly we've doubled, but there's lots Luxoft, if I recall correctly, was the Japanese business. We still launch on long distance. So Chase data from Kantar for that, which is the home of [1.7 million]. So it was a time when somebody else puts in a pocket of the action that a higher proportion of animals surviving longer. And also you see a depletion of the palladium upfront at some time. So that was key for us to So ultimately do all the work necessary to start the study, it's because we can go upfront. It was known to frontline patients be we hope to be able to actually have ultimately prove efficacy, although this study was predominantly a safety study on C. hook, just that some people are going to be disappointed that some people somewhere in the world will start to do it on Romley and we would we simply noted above, we pulse that better than anybody else. So that so sorry to be again, completion data, but I'm pleased so far.

鮑勃，我們在我們認為如果我們放置附屬機構就能獲得利益的地方。我們的更換零件將依賴一個人，也許開始推出作為一個非常好的例子，這對消費者來說是新的。我們有一整套的臨床前研究。這是幾年前發生的事情，現在一個債券借貸世界被銀行打來的電話搶走了。看看，是否有不同的方法來分割資助的內在活動的問題。這就是我們對南方一些地區進行改造的原因之一，這些地區的資金流最終發生了骨髓纖維化。從我們所看到的結果來看，我們的吞吐量實際上只增加了一倍，但如果我沒記錯的話，有很多 Luxoft 是日本業務。我們仍然進行長距離發射。因此，請從 Kantar 獲取數據，這是[170萬]。因此，當時有人採取行動，讓更高比例的動物存活更久。而且有時您會看到鈀金會提前耗盡。所以這對我們來說至關重要，最終完成開始研究所需的所有工作，因為我們可以提前進行。第一線患者都知道，我們希望能夠最終證明療效，儘管這項研究主要是針對鉤狀鉤蟲的安全性研究，只是有些人會對世界上某個地方的某些人開始感到失望在羅姆利上做到這一點，我們會在上面簡單指出，我們比其他任何人都更能把握這一點。所以很抱歉再次完成數據，但到目前為止我很高興。

Well, the rationale the same with a in a mouse, a terrible disease relapse refractory patient hub for Vertex and rations on the other one of Ensemble, I hope for these patients, but also for 12 months, I've read it all to that. Our goal is really patients ongoing. So if we do something reasonably on a weighted average occupancy for our ultimate when you file for an offshore property production that's pretty positive in separate sort of in London, but advantageous product mix such.

好吧，基本原理與小鼠中的相同，一種可怕的疾病復發難治性患者中心 Vertex 和口糧在另一個 Ensemble 上，我希望這些患者，但也有 12 個月，我已經讀完了這一切。我們的目標是讓患者真正持續下去。因此，當您申請離岸房地產生產時，如果我們對最終的加權平均入住率採取合理的措施，這在倫敦的單獨類型中非常積極，但具有有利的產品組合。

I appreciate the comments.

我很欣賞這些評論。

Thanks.

謝謝。

So and again, if you'd like to ask your question, press star one on your telephone keypad.

一次又一次，如果您想提出問題，請按電話鍵盤上的星號一。

Your next question comes from the line of Gil Blum from 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。

Yes, hi, this is Mark housekeeping on per gallon. Thank you for taking our question on first one would be how much I know you've touched on this before, but how much extra effort do you think you'll have to spend on educating community physicians on managing cytopenias versus academic ones, assuming approval? And then do you have any thoughts on how the recent data from more focus at ASH could impact the myelofibrosis landscape and any future development in this space?

是的，嗨，這是馬克每加侖的客房服務。感謝您回答我們的第一個問題，我知道您之前已經接觸過這個問題多少，但是如果獲得批准，您認為您需要花費多少額外的努力來教育社區醫生管理血球減少症與學術治療？那麼您對 ASH 的最新數據如何影響骨髓纖維化景觀以及該領域的未來發展有何想法？

Thank you.

謝謝。

As we pace tailor made for annual growth and more.

我們的步伐是為年度成長等量身定制的。

Sure.

當然。

So we have had extensive discussions with both community and academic providers. And just as a reminder for everyone, lower-risk MDS is predominantly treated within the community setting. Physicians tell us they have deep experiences with drugs such as Len HMAs and are very adept at managing our HIM related side effects for patients and for them the point to prolong myelo suppression with HMAs, et cetera, as areas which they have managed successfully for a long period of time with imetelstat in particular, what is really important is our which Madacy really favorably is the predictability of the cytopenias, the fact that the cytopenias typically are a finite duration and tend to go away and by cycle two and cycle three. And also importantly, there are no clinical consequences associated with the cytopenias in terms of infections and hospitalizations and bleeding events on. And when we also provide context on the mechanism of action, this is something that's received very favorably by the practicing hematologist. So we do not see much differences between the community versus the academic hematologists in terms of their perceptions and management of toxicities. They are adept with their training and also their practice experiences.

因此，我們與社區和學術提供者進行了廣泛的討論。提醒大家的是，低風險 MDS 主要在社區環境中接受治療。醫生告訴我們，他們對 Len HMA 等藥物有豐富的經驗，並且非常擅長為患者管理 HIM 相關副作用，對他們來說，延長 HMA 等骨髓抑制的意義在於，他們已經成功管理了多年的領域尤其是長時間使用imetelstat，真正重要的是我們的Madacy 真正有利的是血球減少的可預測性，事實上血球減少通常是有限的持續時間，並且往往會在第二週期和第三週期消失。同樣重要的是，在感染、住院和出血事件方面，不存在與血球減少相關的臨床後果。當我們也提供作用機制的背景資訊時，這會受到執業血液學家的歡迎。因此，我們認為社區和學術血液學家在對毒性的看法和管理方面沒有太大差異。他們熟悉他們的訓練和實踐經驗。

With regards to the question on myelofibrosis. I think this is also an area which is fast moving and we will obviously wait to see what happens with the BCL-2 and the BET inhibitors in terms of entering the landscape. But a reminder forward myelofibrosis is that we are the only Phase three study, the largest effort to the best of my knowledge in the world, which is looking at survival in a patient population that's relapsed and refractory to diagnose this patient population is extremely underserved. And every and feedback from physicians, academic experts leading KOLs is that if our myelofibrosis study is positive, it is going to be transformative for patients with myelofibrosis and really will be rapidly well adopted within the.

關於骨髓纖維化的問題。我認為這也是一個快速發展的領域，我們顯然會等待 BCL-2 和 BET 抑制劑進入市場後會發生什麼。但骨髓纖維化的一個提醒是，我們是唯一的第三階段研究，這是據我所知世界上最大的努力，該研究正在研究復發和難治性患者群體的生存情況，以診斷該患者群體的服務極為不足。來自醫生、學術專家和 KOL 的回饋是，如果我們的骨髓纖維化研究是正面的，它將對骨髓纖維化患者產生革命性的影響，並且真的很快就會被廣泛採用。

So I'll just stop here.

所以我就停在這裡。

Thank you.

謝謝。

Your next question comes from the line of Joel Beatty from Baird.

您的下一個問題來自貝爾德 (Baird) 的喬爾·比蒂 (Joel Beatty)。

Your line is open and thanks for taking the questions and for the early access program to provide any updates or clarify how many patients are a part of it?

您的熱線已開通，感謝您提出問題並感謝早期訪問計劃提供任何更新或澄清有多少患者參與其中？

Tim, do you want me to take that?

提姆，你想讓我接受嗎？

Sorry, Jan, go ahead on somebody.

抱歉，Jan，請繼續某人。

So that's a clinical study, Joel, we do not provide updates on the enrollment, et cetera. Projections within that space up in the study is ongoing.

所以這是一項臨床研究，喬爾，我們不提供註冊等方面的最新資訊。研究中對此空間的預測正在進行中。

Kevin, thanks for the guidance of the cash runway into Q3 2025 what sales assumptions are going into that guidance?

Kevin，感謝您對 2025 年第三季現金跑道的指導，該指導包含哪些銷售假設？

I'm sorry a on Neon, Tom. We have not made any bones, so sorry, and we haven't shared any sales guidance or revenue guidance just yet, Kevin, thank you.

湯姆，我很抱歉霓虹燈。我們還沒有做出任何決定，很抱歉，我們還沒有分享任何銷售指導或收入指導，凱文，謝謝。

Yes, and we have reached the end of our question and answer period. I will now turn the call back over to Aron Feingold for some final closing remarks.

是的，我們的問答期已經結束了。現在，我將把電話轉回給 Aron Feingold，讓其做最後的總結發言。

Thank you, everyone so much for joining us today. We appreciate your interest in Geron and look forward to keeping you updated Be well.

非常感謝大家今天加入我們。我們感謝您對 Geron 的興趣，並期待為您提供最新消息。

This concludes today's conference call. Thank you for your participation. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。