Geron Corp (GERN) 2022 Q4 法說會逐字稿

Good afternoon. My name is Emma, 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 2022 Conference Call.

下午好。我叫艾瑪，今天我將擔任你們的會議接線員。此時，我想歡迎大家參加 Geron Corporation 的第四季度和全年 2022 年電話會議。

(Operator Instructions)

（操作員說明）

Thank you. Aron Feingold, VP of Investor Relations and Corporate Communications. You may begin your conference.

謝謝。投資者關係和企業傳播副總裁 Aron Feingold。你可以開始你的會議。

Good afternoon, everyone. Welcome to the Geron Corporation Fourth Quarter and Year-End 2022 Earnings Conference Call. I am Aron Feingold, Geron's Vice President of Investor Relations and Corporate Communications. I'm joined today by the following members of Geron's management team. Dr. John Scarlett, Chairman and Chief Executive Officer; Olivia Bloom, Executive Vice President and Chief Financial Officer; Dr. Faye Feller, Executive Vice President and Chief Medical Officer; and Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer.

大家下午好。歡迎來到 Geron Corporation 2022 年第四季度和年終收益電話會議。我是 Geron 的投資者關係和企業傳播副總裁 Aron Feingold。今天，Geron 管理團隊的以下成員加入了我的行列。董事長兼首席執行官 John Scarlett 博士； Olivia Bloom，執行副總裁兼首席財務官；執行副總裁兼首席醫療官 Faye Feller 博士；以及企業戰略執行副總裁兼首席商務官 Anil Kapur。

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 fact.

在我們開始之前，請注意，在本次演示和問答環節中，我們將就未來事件、業績、計劃、預期和其他預測做出前瞻性陳述，包括與治療潛力和imetelstat 的潛在監管批准、預期的臨床和商業事件及相關時間表、Geron 財務資源的充足性和其他非歷史事實的陳述。

Actual events or results could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Geron's annual report on Form 10-K for the year ended December 31, 2022, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements.

實際事件或結果可能存在重大差異。因此，我建議您參考 Geron 截至 2022 年 12 月 31 日止年度的 10-K 表格年度報告中“風險因素”標題下的討論，其中確定了可能導致實際結果與前瞻性結果大不相同的重要因素-尋找陳述。

Geron undertakes no duty or obligation to update our forward-looking statements. Please refer to the press release and slide deck for today's call under Events in the Investors & Media section of our website at www.geron.com/investors for our fourth quarter and annual 2022 financial results as well as business updates and expected upcoming key milestones. The agenda for today's conference call will be as follows. Chip will provide introductory remarks.

Geron 不承擔更新我們的前瞻性陳述的責任或義務。請參閱我們網站 www.geron.com/investors 上“投資者與媒體”部分“活動”下今天電話會議的新聞稿和幻燈片，了解我們的第四季度和 2022 年年度財務業績以及業務更新和預期即將到來的關鍵里程碑.今天電話會議的議程如下。 Chip 將提供介紹性發言。

Faye will highlight key data from the recent topline results from IMerge Phase III and provide a status update on our regulatory plans. She will also discuss our other ongoing development programs.

Faye 將重點介紹 IMerge III 期最新頂線結果的關鍵數據，並提供我們監管計劃的最新狀態。她還將討論我們正在進行的其他開發計劃。

Anil will discuss this year's planned commercial preparedness activities. Olivia will review fourth quarter and year-end 2022 financial results, financial guidance for 2023 and current capital resources, and Chip will provide concluding remarks before going to the Q&A session.

Anil 將討論今年計劃的商業準備活動。 Olivia 將回顧 2022 年第四季度和年底的財務業績、2023 年的財務指導和當前的資本資源，Chip 將在進入問答環節之前發表總結性意見。

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

有了這個，我會把電話轉給 Chip。芯片？

Thanks, Aron. Good afternoon, everyone. Thanks for joining us today. With positive topline results from IMerge Phase III in hand, we now have a charted path towards several potentially significant regulatory and commercial catalysts which we expect will further enhance the value of imetelstat. Building on the momentum created by the lower-risk MDS results, we are also advancing our pipeline to expand the potential applications for imetelstat and telomerase inhibition, which we envision will establish Geron as a leader in the treatment of hematologic malignancies.

謝謝，阿倫。大家下午好。感謝您今天加入我們。憑藉手頭 IMerge III 期的積極頂線結果，我們現在有了通往幾個潛在重要監管和商業催化劑的圖表路徑，我們預計這將進一步提高 imetelstat 的價值。基於低風險 MDS 結果所產生的勢頭，我們還在推進我們的管道，以擴大 imetelstat 和端粒酶抑制的潛在應用，我們設想這將使 Geron 成為治療血液系統惡性腫瘤的領導者。

As a first step, in the commercially attractive lower-risk MDS indication, we remain on track to submit the NDA in mid-2023 and to complete the MAA submission in the second half of 2023. In parallel, we're preparing for a potential U.S. commercial launch in the first half of 2024 and a potential EU launch by the end of 2024. We recently expanded our capabilities to support the potential commercialization of imetelstat with the hiring of seasoned professionals with deep operational and launch experience. These individuals who will serve on our growing senior commercial leadership team, include experts in trade and channel relations, market access, marketing, medical affairs and sales.

作為第一步，在具有商業吸引力的低風險 MDS 適應症中，我們仍有望在 2023 年年中提交 NDA 並在 2023 年下半年完成 MAA 提交。與此同時，我們正在準備潛在的2024 年上半年在美國商業發布，並可能在 2024 年底前在歐盟推出。我們最近擴大了我們的能力，以支持 imetelstat 的潛在商業化，聘請了具有豐富運營和發布經驗的經驗豐富的專業人員。這些人將加入我們不斷壯大的高級商業領導團隊，包括貿易和渠道關係、市場准入、市場營銷、醫療事務和銷售方面的專家。

We believe that adding these colleagues who are already highly talented employee base, provides the expertise and experience necessary to prepare for the anticipated commercial launch of imetelstat. A key differentiating quality of imetelstat and its novel telomerase inhibition mechanism of action is the potential to modify the course of the underlying hematologic malignancy. The compelling Phase III readout in lower-risk MDS has now added to our robust body of evidence of disease modification.

我們相信，加入這些已經是非常有才華的員工基礎的同事，可以提供必要的專業知識和經驗，為 imetelstat 的預期商業發布做準備。 imetelstat 及其新型端粒酶抑製作用機制的一個關鍵差異化特性是有可能改變潛在的血液惡性腫瘤的病程。低風險 MDS 中令人信服的 III 期結果現已添加到我們強大的疾病緩解證據中。

And we believe our other clinical and research programs will further corroborate the potential meaningful clinical benefits with imetelstat treatment. In our second imetelstat Phase III trial, IMpactMF, a potential positive overall survival outcome could set the stage for changing the treatment landscape in myelofibrosis. Based on our current planning assumptions for enrollment and event rates, we expect an interim analysis for OS in IMpactMF in 2024.

我們相信我們的其他臨床和研究項目將進一步證實 imetelstat 治療的潛在有意義的臨床益處。在我們的第二個 imetelstat III 期試驗 IMpactMF 中，潛在的積極總體生存結果可能為改變骨髓纖維化的治療前景奠定基礎。根據我們目前對入組率和事件率的規劃假設，我們預計 2024 年將對 IMpactMF 中的 OS 進行中期分析。

To further assess the potential of imetelstat in other hematologic malignancies, we're advancing development programs, which evaluate imetelstat in additional indications and in combination regimens. We expect significant readouts from these programs over the next several years. We have a strong balance sheet to fuel our regulatory, commercial and imetelstat development activities. On the heels of positive topline results from our IMerge Phase III study in lower-risk MDS, we raised over $210 million in net proceeds from high-quality strategic investors in early January of this year.

為了進一步評估 imetelstat 在其他血液系統惡性腫瘤中的潛力，我們正在推進開發計劃，以評估 imetelstat 在其他適應症和聯合治療方案中的作用。我們期望在未來幾年內從這些計劃中獲得重要的信息。我們擁有強大的資產負債表來推動我們的監管、商業和 imetelstat 開發活動。在我們的 IMerge III 期低風險 MDS 研究取得積極的頂線結果之後，我們在今年 1 月初從優質戰略投資者那裡籌集了超過 2.1 億美元的淨收益。

Combining our year-end cash balance, with the net proceeds from a successful financing in January and the warrant exercise proceeds received in the first 2 months of this year, we accumulated total cash holdings in excess of $445 million. We believe that these capital resources will be sufficient to fund our projected operating requirements through the end of the third quarter of 2025, supporting the achievement of many of the value accreting catalysts we're pursuing.

結合我們年終的現金餘額，加上 1 月份成功融資的淨收益以及今年前兩個月收到的認股權證行權收益，我們累計持有的現金總額超過 4.45 億美元。我們相信，這些資本資源將足以滿足我們到 2025 年第三季度末的預計運營需求，支持實現我們正在追求的許多價值增值催化劑。

In parallel with our continuing preparations to commercialize imetelstat, we continue to consider relationships with potential partners, including exploration of regional and other deal structures of possible mutual interest, which could potentially maximize the value of imetelstat for patients and Geron shareholders. In summary, the commercial preparedness and clinical development activities planned in 2023 as well as potential upcoming catalysts are expected to position Geron to become a leader in the treatment of heme malignancies.

在我們繼續準備將 imetelstat 商業化的同時，我們繼續考慮與潛在合作夥伴的關係，包括探索可能具有共同利益的區域和其他交易結構，這可能會最大化 imetelstat 對患者和 Geron 股東的價值。總之，計劃於 2023 年開展的商業準備和臨床開發活動以及即將推出的潛在催化劑有望使 Geron 成為治療血紅素惡性腫瘤的領導者。

Further, our strong financial position and highly capable employee base provides the foundation for Geron to become a fully integrated commercial biotech company over the next 15 months.

此外，我們強大的財務狀況和高素質的員工基礎為 Geron 在未來 15 個月內成為一家完全整合的商業生物技術公司奠定了基礎。

With that, let me hand the call over to Faye Feller, our Chief Medical Officer. Faye?

有了這個，讓我把電話轉給我們的首席醫療官 Faye Feller。王菲？

Thank you, Chip, and good afternoon to everyone on the call. We were thrilled and very proud to report positive topline results from our IMerge Phase III study of imetelstat in lower-risk MDS in the beginning of January. On our January conference call, we presented detailed efficacy and safety results, which are available on the IR section of our website under Presentation.

謝謝 Chip，電話會議中的每個人下午好。我們很高興也非常自豪地報告了我們在 1 月初對低風險 MDS 中的 imetelstat 進行的 IMerge III 期研究的積極頂線結果。在我們 1 月份的電話會議上，我們展示了詳細的有效性和安全性結果，這些結果可在我們網站的 IR 部分的演示文稿下找到。

Today, I will provide a high-level summary of those results, which we believe confirms a positive overall benefit/risk profile for imetelstat. We saw statistically significant and clinically meaningful improvements in the imetelstat-treated patients compared to the placebo control arm. Specifically, the trial met its primary endpoint of 8-week transfusion independence as well as a secondary 24-week TI endpoint.

今天，我將提供這些結果的高級摘要，我們認為這證實了 imetelstat 的積極整體收益/風險狀況。與安慰劑對照組相比，我們看到接受 imetelstat 治療的患者有統計學意義和臨床意義的改善。具體而言，該試驗達到了 8 週輸血獨立性的主要終點以及 24 週 TI 次要終點。

We saw substantial increases in both hemoglobin levels and reductions in transfusions. We also saw efficacy across MDS subtypes, including both RS+ and RS- patients and irrespective of baseline transfusion burden or IPSS risk category. The initial clinical and molecular evidence we reported support imetelstat's potential for MDS disease modification. And the safety results were consistent with prior imetelstat's clinical experience. The most frequent adverse events were neutropenia and thrombocytopenia, which were manageable and reversible with the majority being resolved in less than 4 weeks.

我們看到血紅蛋白水平顯著增加，輸血減少。我們還看到了跨 MDS 亞型的療效，包括 RS+ 和 RS- 患者，無論基線輸血負擔或 IPSS 風險類別如何。我們報告的初步臨床和分子證據支持 imetelstat 改善 MDS 疾病的潛力。並且安全性結果與之前imetelstat的臨床經驗一致。最常見的不良事件是中性粒細胞減少症和血小板減少症，這是可控和可逆的，大多數在不到 4 週內得到解決。

Importantly, any serious clinical consequences from these cytopenias with imetelstat treatment were observed at low rates and were similar to placebo. We are planning to present and publish additional data and analyses from IMerge throughout 2023 as we have been collaborating with key opinion leaders to prepare these abstracts and discussing the topline results with providers. We have received excellent feedback on the readout as well as acknowledgment on the potential for imetelstat to represent a meaningful treatment advance in lower-risk MDS.

重要的是，imetelstat 治療引起的這些血細胞減少引起的任何嚴重臨床後果發生率很低，並且與安慰劑相似。我們計劃在整個 2023 年展示和發布來自 IMerge 的更多數據和分析，因為我們一直在與主要意見領袖合作準備這些摘要並與供應商討論重要結果。我們收到了關於讀數的極好反饋，以及對 imetelstat 代表低風險 MDS 有意義的治療進展的潛力的認可。

Based on these positive topline results from IMerge Phase III, we continue to execute on our plan to submit an NDA in mid-2023. Since our request for rolling submission was granted, we have submitted the non-clinical module of the NDA this quarter. We remain on track with our plan to submit the remaining modules, including clinical and CMC by mid-year. Also this quarter, we participated in a standard pre-NDA meeting with the FDA. There were no showstoppers at that meeting, nor comments that change our expected timeline or fundamental strategy for the NDA submission.

基於 IMerge III 期的這些積極的頂線結果，我們繼續執行我們的計劃，在 2023 年年中提交 NDA。由於我們的滾動提交請求獲得批准，我們已在本季度提交了 NDA 的非臨床模塊。我們繼續按計劃在年中之前提交剩餘的模塊，包括臨床和 CMC。同樣在本季度，我們參加了與 FDA 舉行的標準 NDA 前會議。在那次會議上沒有任何阻礙，也沒有改變我們預期的時間表或 NDA 提交的基本策略的評論。

When we submit the NDA, we plan to request priority review as allowed under our Fast Track designation in lower-risk MDS. If granted, we expect FDA approval of the NDA and the U.S. commercial launch of imetelstat in lower-risk MDS could occur as early as the first quarter of 2024. In addition, the MAA submission is planned by the end of 2023.

當我們提交 NDA 時，我們計劃根據我們在低風險 MDS 中的快速通道指定要求進行優先審查。如果獲得批准，我們預計 FDA 批准 NDA 並在美國商業推出低風險 MDS 中的 imetelstat 最早可能在 2024 年第一季度發生。此外，計劃在 2023 年底提交 MAA。

Typically, the review time for an MAA is up to 14 months. Thus, we expect the timing of potential approval of the MAA by the end of 2024. Please note, going forward, we don't plan to provide any details relating to regulatory interactions, unless they result in a change to our submission strategy or expected timing.

通常，MAA 的審查時間最長為 14 個月。因此，我們預計 MAA 可能在 2024 年底獲得批准的時間。請注意，今後我們不打算提供任何與監管互動相關的細節，除非它們導致我們的提交策略或預期發生變化定時。

Moving on to our second Phase III clinical program. Let me outline our plans in 2023 for relapsed/refractory MF. IMpactMF is the first and only Phase III MF trial with overall survival as the primary endpoint. To trigger the interim analysis for this study, death events need to occur in more than 35% of the total planned enrollment of 320 patients. Thus, the timing of the interim analysis depends on the number of enrolled patients as well as the rate at which death events occur.

繼續我們的第二個 III 期臨床計劃。讓我概述一下我們在 2023 年針對複發/難治性 MF 的計劃。 IMpactMF 是第一個也是唯一一個以總生存期為主要終點的 III 期 MF 試驗。要觸發本研究的中期分析，死亡事件需要發生在 320 名計劃入組患者總數的 35% 以上。因此，中期分析的時間取決於入組患者的數量以及死亡事件的發生率。

Potentially, the number of events required to conduct the interim analysis for this study could occur before enrollment is complete as these death events will accrue throughout the enrollment period. Using current planning assumptions around enrollment and median OS estimates for each treatment arm, we expect the interim analysis for IMpactMF to occur in 2024. These analyses are event-driven, and it is uncertain whether actual rates for enrollment and death events will reflect current assumptions.

潛在地，進行本研究的中期分析所需的事件數量可能會在入組完成之前發生，因為這些死亡事件將在整個入組期間累積。使用當前關於每個治療組的入組率和中位 OS 估計的計劃假設，我們預計 IMpactMF 的中期分析將在 2024 年進行。這些分析是事件驅動的，並且不確定入組率和死亡事件的實際發生率是否會反映當前的假設.

This quarter, we initiated several strategies to increase the rate of site activation and patient enrollment, including recruitment initiatives for patient matching and more engagement with investigators through on-site visits or interactions at medical meetings. We will consider the impact of these initiatives over the next 6 months as well as evaluate the overall rates of enrollment and death events occurring in the study. We expect to provide an update on the projected timing of the interim analysis after that evaluation.

本季度，我們啟動了多項策略來提高站點激活率和患者註冊率，包括患者匹配的招募計劃以及通過現場訪問或醫學會議上的互動與研究人員更多地接觸。我們將在未來 6 個月內考慮這些舉措的影響，並評估研究中發生的總體入組率和死亡事件。我們希望在評估後提供中期分析的預計時間更新。

If the improvement in OS that was observed in imetelstat-treated patients in our IMbark Phase II trial can be confirmed in the Phase III IMpactMF trial, and we believe imetelstat will be strongly differentiated from other treatments in MF, currently approved or in development and will likely change the treatment paradigm for relapsed/refractory MF patients. As a hematologist, I know from personal experience that physicians consider OS as the ultimate measure of benefit for the treatment of their cancer patients.

如果在我們的 IMbark II 期試驗中在接受 imetelstat 治療的患者中觀察到的 OS 改善可以在 III 期 IMpactMF 試驗中得到證實，我們相信 imetelstat 將與目前已批准或正在開發的 MF 的其他治療方法有很大區別，並將可能會改變復發/難治性 MF 患者的治療模式。作為一名血液學家，我從個人經驗中了解到，醫生將 OS 視為癌症患者治療獲益的最終衡量標準。

We expect OS would be especially relevant in the case of IMpactMF patients who no longer respond to JAK inhibitors and who, due to their current dismal prognosis and limited treatment options are in desperate need for novel therapy. Beyond our Phase III trials, we have several additional programs to potentially expand the treatment applications for imetelstat in hematologic malignancies.

我們預計 OS 與不再對 JAK 抑製劑有反應的 IMpactMF 患者以及由於目前預後不良和治療選擇有限而迫切需要新療法的患者特別相關。除了我們的 III 期試驗之外，我們還有幾個額外的項目可能會擴大 imetelstat 在血液系統惡性腫瘤中的治療應用。

In May 2022, we started IMproveMF, a Phase I study designed to evaluate the safety and clinical activity of imetelstat in combination with ruxolitinib in patients with frontline MF. This study design was informed by data from preclinical studies, describing the sequential treatment of ruxolitinib followed by imetelstat has a selective inhibitory effect on malignant MF stem cells of the sparring normal hematopoietic stem cells.

2022 年 5 月，我們啟動了 IMproveMF，這是一項 I 期研究，旨在評估 imetelstat 聯合 ruxolitinib 在一線 MF 患者中的安全性和臨床活性。該研究設計基於臨床前研究的數據，描述了 ruxolitinib 和 imetelstat 的序貫治療對正常造血幹細胞的惡性 MF 幹細胞具有選擇性抑製作用。

For IMproveMF, we aim to determine the safety profile of the combination regimen of ruxolitinib and imetelstat as well as explore any potential for disease-modifying activity in a frontline MF disease setting, similar to what was observed with imetelstat treatment in the Phase II IMbark trial in a relapsed/refractory myelofibrosis patient population. 2 of the 3 trial sites for this study are open for patient enrollment, the remaining site is expected to open for enrollment in 2023.

對於 IMproveMF，我們的目標是確定 ruxolitinib 和 imetelstat 聯合方案的安全性，並探索在一線 MF 疾病環境中改善疾病活動的任何潛力，類似於在 II 期 IMbark 試驗中使用 imetelstat 治療觀察到的情況在復發/難治性骨髓纖維化患者群體中。本研究的 3 個試驗地點中有 2 個已開放患者入組，其餘地點預計將於 2023 年開放入組。

We also expect to present preliminary data from this study by the end of 2023. Based on preclinical models showing imetelstat prevented expansion of human AML leukemic stem cells and prolonged survival in stem cells, we are also supporting an investigator-led study in relapsed/refractory AML and higher-risk MDS for patients who are already treated with a hypomethylating agent. As noted on the slide, this study called IMpress, is evaluating imetelstat as a single-agent treatment in this severe disease. The first site is planned to open in 2023.

我們還希望在 2023 年底之前提供這項研究的初步數據。根據顯示 imetelstat 可防止人類 AML 白血病幹細胞擴增並延長干細胞存活期的臨床前模型，我們還支持一項由研究者主導的複發/難治性研究已經接受去甲基化藥物治療的患者的 AML 和高危 MDS。如幻燈片所示，這項名為 IMpress 的研究正在評估 imetelstat 作為這種嚴重疾病的單藥治療。第一個站點計劃於 2023 年開放。

If the initial IMpress data show promise for imetelstat in higher-risk MDS and AML, we expect to support another investigator-led study, evaluating the combination of imetelstat plus other drugs that are part of the standard of care for such patients.

如果最初的 IMpress 數據顯示 imetelstat 在高風險 MDS 和 AML 中有希望，我們希望支持另一項研究者主導的研究，評估 imetelstat 與其他藥物的組合，這些藥物是此類患者護理標準的一部分。

Moving on to our preclinical and research programs. This slide provides a snapshot of the status of our lymphoid malignancies and next-generation TI programs. In November 2022, early data was published from the pre-clinical programs in lymphoid malignancies being conducted at MD Anderson Cancer Center. Based on these early results, we are continuing the collaboration to assess the potential therapeutic effect of imetelstat in lymphoid malignancies and expect further data by the end of 2023.

繼續我們的臨床前和研究項目。這張幻燈片簡要介紹了我們的淋巴惡性腫瘤和下一代 TI 計劃的狀態。 2022 年 11 月，MD 安德森癌症中心正在進行的淋巴惡性腫瘤臨床前項目發布了早期數據。基於這些早期結果，我們正在繼續合作，以評估 imetelstat 在淋巴惡性腫瘤中的潛在治療效果，並期待在 2023 年底之前獲得更多數據。

The objective of our discovery program is to identify a lead compound as a potential next-generation oral telomerase inhibitor. We continue to investigate various chemical entities as potential scaffolds. We expect completion of the current discovery effort in 2023, upon which we plan to potentially advance any of these compounds into the next step of discovery research. If successful, these efforts would permit initiation of an IND-enabling non-clinical studies in the future.

我們發現計劃的目標是確定一種先導化合物作為潛在的下一代口服端粒酶抑製劑。我們繼續研究各種化學實體作為潛在的支架。我們預計當前的發現工作將在 2023 年完成，屆時我們計劃可能將這些化合物中的任何一種推進到下一步的發現研究中。如果成功，這些努力將允許在未來啟動支持 IND 的非臨床研究。

As I hope you can see the positive topline results in lower-risk MDS have provided an impetus for the next step in imetelstat's development. We believe continued progress in the other areas I described, such as relapsed/refractory MF, frontline MF, higher-risk MDS and AML, lymphoid malignancies and the discovery of potential next-generation telomerase inhibitors, we'll explore how imetelstat and telomerase inhibition may provide potential benefit to many more patients.

我希望您能看到低風險 MDS 的積極頂線結果為 imetelstat 的下一步發展提供了動力。我們相信我描述的其他領域的持續進展，例如復發/難治性 MF、一線 MF、高風險 MDS 和 AML、淋巴惡性腫瘤以及潛在的下一代端粒酶抑製劑的發現，我們將探索 imetelstat 和端粒酶抑製作用可能為更多患者帶來潛在益處。

With that, I will turn the call over to Anil to describe the planned activities around potential commercial launch of imetelstat. Anil?

有了這個，我將把電話轉給 Anil 來描述圍繞 imetelstat 潛在商業發布的計劃活動。阿尼爾？

Thank you, Faye, and good afternoon, everyone. Lower-risk MDS is a highly attractive market with a significant addressable patient population. Given the positive topline results announced earlier this year, we expect imetelstat to be highly differentiated and to be adopted widely in the treatment of lower-risk MDS. We are taking important steps to ensure commercial readiness at launch. As Chip mentioned, we have made multiple senior commercial leadership hires with extensive industry knowledge, launch and operational experience.

謝謝你，Faye，大家下午好。低風險 MDS 是一個極具吸引力的市場，擁有大量可尋址的患者群體。鑑於今年早些時候公佈的積極頂線結果，我們預計 imetelstat 將具有高度差異化，並被廣泛用於治療低風險 MDS。我們正在採取重要步驟以確保在發佈時做好商業準備。正如 Chip 所提到的，我們聘用了多位具有廣泛行業知識、發布和運營經驗的高級商業領導。

Now with our leadership team onboarded, we continue to build out the commercial organization in a phased manner with the goal of hiring talent with deep oncology and U.S. market experience. Our commercial go-to-market strategy revolves around the following fundamental pillars that are focused on successfully transitioning Geron to a commercial stage company and ensuring a successful launch of imetelstat.

現在隨著我們的領導團隊的加入，我們將繼續分階段建立商業組織，目標是招聘具有深厚腫瘤學和美國市場經驗的人才。我們的商業上市戰略圍繞以下基本支柱展開，重點是成功地將 Geron 轉變為商業階段公司，並確保成功推出 imetelstat。

First, on the product front, in addition to our regulatory activities, we are focused on building a comprehensive and integrated clinical and economic value proposition that conclusively outlines imetelstat's benefits to providers, clinics, hospital systems and payers.

首先，在產品方面，除了我們的監管活動外，我們還專注於建立一個全面、綜合的臨床和經濟價值主張，最終概述了 imetelstat 對供應商、診所、醫院系統和付款人的好處。

We expect this messaging to highlight imetelstat's differentiating qualities as seen in the topline results, which include the broad efficacy across MDS subtypes, including both RS+ and RS- patients, the durability of continuous transfusion independence, the totality of clinical benefit, which includes a reduction in transfusion burden and significant increases in hemoglobin levels, the strong evidence of potential disease modification, and what we believe is a favorable benefit risk profile.

我們希望此消息能夠突出 imetelstat 的差異化特性，如頂線結果所示，其中包括跨 MDS 亞型（包括 RS+ 和 RS- 患者）的廣泛療效、持續輸血獨立性的持久性、總體臨床益處，包括減少輸血負擔和血紅蛋白水平的顯著增加，潛在疾病改善的有力證據，以及我們認為有利的收益風險狀況。

Second, we are focused on the long lead time supply chain activities, including state licensing and third-party logistics efforts to facilitate efficient distribution of imetelstat and smooth flow through the U.S. health care system. Third, a key focus for us is on broad engagement with a diverse set of stakeholders, including providers, payers and advocacy groups to seek a favorable reimbursement for imetelstat.

其次，我們專注於長周期供應鏈活動，包括國家許可和第三方物流工作，以促進 imetelstat 的高效分配和美國醫療保健系統的順暢流動。第三，我們的一個關鍵重點是與不同的利益相關者廣泛接觸，包括提供者、支付者和倡導團體，以尋求對 imetelstat 的有利報銷。

To engage with and educate providers, our teams have planned extensive presence at global, national and local hematology scientific meetings to raise awareness of the challenges facing patients with lower-risk MDS. We are also extensively engaged with payers and planning submissions of imetelstat data to major societies, including NCCN and ASCO for their consideration for inclusion in guidelines. In addition, we remain heavily engaged with patient advocacy groups.

為了與提供者接觸並對其進行教育，我們的團隊計劃廣泛參加全球、國家和地方血液學科學會議，以提高人們對低風險 MDS 患者所面臨挑戰的認識。我們還與支付者廣泛接觸，併計劃將 imetelstat 數據提交給主要學會，包括 NCCN 和 ASCO，以供他們考慮納入指南。此外，我們仍然與患者倡導團體保持密切聯繫。

Fourth, our efforts are also focused on Geron's organizational evolution to a commercial entity. This effort involves building and expanding the functions and capabilities across Geron, including information technology, human resources, finance and legal to support Geron's future growth and our commercial ambitions. I look forward to providing updates on commercial activities throughout the year.

第四，我們的努力也集中在Geron向商業實體的組織演變。這項工作涉及建立和擴展整個 Geron 的職能和能力，包括信息技術、人力資源、財務和法律，以支持 Geron 的未來發展和我們的商業抱負。我期待著提供全年商業活動的最新信息。

Now I'll turn the call over to Olivia for a financial update. Olivia?

現在我會把電話轉給 Olivia 以獲取最新的財務信息。奧利維亞？

Thanks, Anil, and thanks to everyone on the call for joining us today. Please refer to the press release we issued this afternoon, which is available on our website for detailed financial results. As expected, overall operating expenses for the fourth quarter and full year 2022 were higher than the same period in 2021. Total operating expenses for the 3 and 12 months ended December 31, 2022, were $42.1 million and $139.1 million, respectively, compared to $32 million and $115.4 million for the same period in 2021. The increase in research and development expenses primarily reflects higher personnel-related expenses for additional headcount and increased consulting costs related to preparation for topline results and regulatory submissions in lower-risk MDS.

謝謝 Anil，也感謝今天來電的所有人。請參閱我們今天下午發布的新聞稿，該新聞稿可在我們的網站上獲取，了解詳細的財務結果。正如預期的那樣，2022 年第四季度和全年的總體運營費用高於 2021 年同期。截至 2022 年 12 月 31 日的三個月和十二個月的總運營費用分別為 4210 萬美元和 1.391 億美元，而同期為 32 美元百萬美元和 2021 年同期分別為 1.154 億美元。研發費用的增加主要反映了與人員相關的人員相關費用增加，以及與準備頂線結果和低風險 MDS 的監管提交相關的諮詢費用增加。

The increase in general and administrative expenses primarily reflects increased costs for commercial preparatory activities, higher personnel-related expenses for additional headcount and our portion of settlement costs related to the class action and derivative lawsuits.

一般和行政費用的增加主要反映了商業準備活動成本的增加、額外員工的人事相關費用增加以及我們與集體訴訟和衍生訴訟相關的部分和解費用。

For fiscal year 2023, we expect non-GAAP total expenses in the range of approximately $200 million to $210 million. The fiscal year 2023 guidance reflects costs to support planned regulatory submissions in 2023, ongoing clinical trials, IMerge Phase III, IMpactMF, IMproveMF and IMpress as well as preclinical studies in lymphoid malignancies and discovery research for next-generation telomerase inhibitor, manufacturing commercial inventory for imetelstat, preparation for potential U.S. commercial launch of imetelstat in lower-risk MDS and projected increases in headcount as well as interest payments on outstanding debt.

對於 2023 財年，我們預計非 GAAP 總支出在約 2 億美元至 2.1 億美元之間。 2023 財年指南反映了支持計劃在 2023 年提交的監管文件、正在進行的臨床試驗、IMerge III 期、IMpactMF、IMproveMF 和 IMpress 以及淋巴惡性腫瘤的臨床前研究和下一代端粒酶抑製劑的發現研究、製造商業庫存的成本imetelstat，為在低風險 MDS 中潛在的美國商業推出 imetelstat 做準備，並預計增加員工人數以及未償還債務的利息支付。

The fiscal year 2023 financial guidance is based on a set of assumptions. If those assumptions are updated later in the year due to changes in our plans, including in response to potential revised timing of FDA approval and potential U.S. commercial launch of imetelstat in lower-risk MDS, then we plan to update guidance at that time.

2023 財年財務指南基於一系列假設。如果這些假設在今年晚些時候由於我們計劃的變化而更新，包括響應 FDA 批准的潛在修訂時間和美國可能在低風險 MDS 中商業推出 imetelstat，那麼我們計劃在那時更新指南。

As of December 31, 2022, we had approximately $173.1 million in cash, cash equivalents, restricted cash and current and non-current marketable securities. On January 10, 2023, we closed our underwritten public offering for net cash proceeds of approximately $213.3 million after deducting the underwriting discounts and other offering expenses. In addition, in January and February 2023, we have received $59.8 million in cash proceeds from the exercise of outstanding warrants. As a result, we accumulated total cash holdings in excess of $445 million.

截至 2022 年 12 月 31 日，我們擁有約 1.731 億美元的現金、現金等價物、受限制的現金以及流動和非流動有價證券。 2023 年 1 月 10 日，我們在扣除承銷折扣和其他發行費用後，完成了承銷的公開發行，淨現金收益約為 2.133 億美元。此外，在 2023 年 1 月和 2 月，我們通過行使未償認股權證獲得了 5980 萬美元的現金收益。因此，我們累計持有的現金總額超過 4.45 億美元。

Based on our current operating plan and our expectations regarding the timing of the submission and potential acceptance and approval of our planned NDA by the FDA and the potential commercialization in the U.S. for the use of imetelstat in adult patients with lower-risk MDS, we believe that our existing capital resources will be sufficient to fund our projected operating requirements through the end of the third quarter of 2025, which includes potential U.S. commercial launch of imetelstat in lower-risk MDS in the first half of 2024.

根據我們目前的運營計劃和我們對 FDA 對我們計劃的 NDA 的提交時間和潛在接受和批准的預期，以及在美國使用 imetelstat 治療低風險 MDS 成年患者的潛在商業化，我們相信我們現有的資本資源將足以滿足我們到 2025 年第三季度末的預計運營需求，其中包括 2024 年上半年可能在美國商業推出低風險 MDS 中的 imetelstat。

With that, I will now turn the call over to Chip for closing remarks. Chip?

有了這個，我現在將把電話轉給 Chip 作結束語。芯片？

Thanks, Olivia. Geron has made remarkable progress over the last few years and especially in the past 6 months. We look forward to completing the regulatory approval and commercial launch activities now underway and hopefully, to seeing imetelstat become part of the standard of care in lower-risk MDS. We also expect imetelstat will potentially become part of the standard of care in relapsed/refractory myelofibrosis if the IMpactMF study has a positive readout either at the interim analysis expected in 2024 or at the final analysis expected in 2025.

謝謝，奧利維亞。 Geron 在過去幾年取得了顯著進步，尤其是在過去 6 個月裡。我們期待完成目前正在進行的監管批准和商業啟動活動，並希望看到 imetelstat 成為低風險 MDS 護理標準的一部分。我們還預計，如果 IMpactMF 研究在預計於 2024 年進行的中期分析或預計在 2025 年進行的最終分析中有積極的讀數，imetelstat 將有可能成為複發/難治性骨髓纖維化護理標準的一部分。

As we transition from a clinical stage to a commercial stage company, we have never been more excited by our vision of Geron becoming a leader in the treatment of hematologic malignancies and in doing so, positively impacting the lives of patients with these diseases.

當我們從臨床階段過渡到商業階段公司時，我們對 Geron 成為血液系統惡性腫瘤治療領域的領導者並在此過程中積極影響這些疾病患者的生活的願景感到無比興奮。

Thank you for your continued interest and support of imetelstat and Geron, and we'll be glad to take your questions.

感謝您一直以來對 imetelstat 和 Geron 的關注和支持，我們很樂意回答您的問題。

(Operator Instructions)

（操作員說明）

Your first question today comes from the line of Kalpit Patel with B. Riley.

您今天的第一個問題來自 Kalpit Patel 與 B. Riley 的對話。

Maybe one on the Phase III IMpactMF study in the relapsed/refractory myelofibrosis. Can you give us a little more color on how the enrollment is progressing in that trial? Maybe what percentage of patients have actually been enrolled if you have that info available?

也許是關於復發/難治性骨髓纖維化的 III 期 IMpactMF 研究。你能給我們更多關於該試驗的註冊進展情況的信息嗎？如果您有可用的信息，也許實際登記的患者百分比是多少？

Kalpit, it's Chip. I think, Faye will take most of the clinical questions. Go ahead, Faye.

卡爾皮特，是奇普。我認為，Faye 會回答大部分臨床問題。來吧，法伊。

Thanks, Kal. As we mentioned in the prepared remarks, we still expect the interim analysis in 2024 based on our current perception. And we will announce when we've reached 50% enrollment.

謝謝，卡爾。正如我們在準備好的評論中提到的，我們仍然希望根據我們目前的看法在 2024 年進行中期分析。我們將在註冊人數達到 50% 時宣布。

Okay. Okay. And then maybe a couple on the earlier stage improved MF trial. Are you planning to maybe release all of the data from Part 1 in -- by the end of 2023, I believe you mentioned.

好的。好的。然後可能有一對夫婦在早期階段改進了 MF 試驗。您是否計劃在 2023 年底之前發布第 1 部分的所有數據，我相信您提到過。

We're currently focused on continuing to open sites in accrued patients. We will open the third site by the end of the year and are -- will present a data readout guidance later on at that time.

我們目前專注於繼續在應計患者中開設網站。我們將在今年年底前開設第三個網站，屆時將提供數據讀出指南。

Okay. Okay. And maybe one more question on that trial. I think the protocol requires, in Part 1, the use of ruxolitinib for at least 12 weeks prior to enrollment. I guess is that, in any sense, impact how you're viewing the efficacy bar for this trial, this open-label study? I'm just trying to get a sense of if it's fair to make comparisons to historical efficacy with rux.

好的。好的。也許還有一個關於該試驗的問題。我認為協議要求在第 1 部分中，在入組前至少使用 ruxolitinib 12 週。我想，從某種意義上說，這會影響您如何看待這項試驗、這項開放標籤研究的療效標準嗎？我只是想了解將 rux 與歷史功效進行比較是否公平。

Thanks for the question. Really, the purpose of the trial is to assess safety and the lead-in period for the ruxolitinib use is supported by pre-clinical data we have, showing sequential use of ruxolitinib and then imetelstat has the potential for more efficacy. But it also allows us to enroll patients on a stable dose of ruxolitinib. So that we have a better understanding of any additional toxicities when we add imetelstat and the safety profile once imetelstat is added. So it's really meant more for a safety perspective.

謝謝你的問題。實際上，該試驗的目的是評估安全性，我們擁有的臨床前數據支持使用 ruxolitinib 的導入期，表明順序使用 ruxolitinib，然後使用 imetelstat 有可能獲得更高的療效。但它也使我們能夠讓患者接受穩定劑量的 ruxolitinib。這樣我們就可以更好地了解添加 imetelstat 時的任何其他毒性以及添加 imetelstat 後的安全性概況。因此，從安全角度來看，這實際上意味著更多。

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

你的下一個問題來自 Stephen Willey 與 Stifel 的合作。

Can you talk about the site overlap between IMpactMF and IMerge and just whether or not you've seen any tick-up in enrollment following the positive IMerge data disclosure earlier this year.

您能否談談 IMpactMF 和 IMerge 之間的站點重疊，以及您是否看到今年早些時候 IMerge 積極數據披露後的註冊人數有所增加。

Yes. Thanks for the question. We have seen -- after the release of the topline results for IMerge, we have seen an increased interest in IMpactMF and in IMproveMF and just general positive feedback regarding both of the studies in major medical centers. There may be overlap in the sites, but they're -- it's -- both are global studies, and there are plenty of sites for both.

是的。謝謝你的問題。我們已經看到——在 IMerge 的頂線結果發布後，我們看到人們對 IMpactMF 和 IMproveMF 的興趣增加，以及對主要醫療中心的兩項研究的普遍積極反饋。這些網站可能有重疊，但它們——確實——都是全球研究，而且兩者都有很多網站。

Okay. And then -- can you maybe just provide some additional color around the cadence of incremental IMerge data that we should expect to see over the course of this year? And I guess, should we expect the patient reported outcomes data to be included in the next medical conference presentation.

好的。然後——您能否提供一些關於增量 IMerge 數據節奏的額外顏色，我們應該期望在今年看到這些數據？我想，我們是否應該期望患者報告的結果數據包含在下一次醫學會議的報告中。

Sure. We do plan to present the additional data at medical meetings and also plan to submit the data for publication. So we do expect to report patient-reported outcomes in the near future.

當然。我們確實計劃在醫學會議上展示額外的數據，併計劃提交數據以供發表。因此，我們確實希望在不久的將來報告患者報告的結果。

Okay. And then maybe just lastly for Olivia, you provided cash runway guidance through the third quarter of '25. Does this guidance assume that the second tranche of warrants are also exercised? I think that these get triggered on the basis of FDA accepting the NDA filing in lower-risk MDS.

好的。然後也許最後是奧利維亞，你在 25 年第三季度提供了現金跑道指導。本指南是否假設第二批認股權證也已行使？我認為這些是在 FDA 接受低風險 MDS 的 NDA 備案的基礎上觸發的。

Steve, thanks for the question. No. The guidance does not include that. So it would extend the runway further if those proceeds would be received. So the guidance to the end of third quarter 2025 is just what is currently on the balance sheet after the financing and after what's been received so far from exercised warrants.

史蒂夫，謝謝你的提問。不，指南不包括這一點。因此，如果收到這些收益，它將進一步延長跑道。因此，到 2025 年第三季度末的指引正是融資後資產負債表上目前的情況以及迄今為止從行使認股權證收到的情況。

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

你的下一個問題來自 Joel Beatty 與 Baird 的對話。

First one is, are you able to share any feedback from FDA on their openness to filing with priority review?

第一個問題是，您能否分享 FDA 關於他們對提交優先審查持開放態度的任何反饋？

Sure, I'll take that really quickly, and then Faye can add if she has anything. Joel, it's Chip. FDA generally does not give any insights. And generally, we rarely ask regarding insights into priority versus standard review. The answer would almost always be that's a review issue. .

當然，我會很快接受，然後 Faye 有什麼可以補充的。喬爾，是奇普。 FDA 通常不提供任何見解。通常，我們很少詢問有關優先審查與標準審查的見解。答案幾乎總是這是一個審查問題。 .

As you know, they first have to look at the NDA submission and accept it for filing, and that generally takes 60 days. And then at the time that they accept it for filing if they do, then that's when they tell us whether we'll have a priority or a standard review.

如您所知，他們首先必須查看 NDA 提交並接受備案，這通常需要 60 天。然後在他們接受提交時，如果他們這樣做了，他們就會告訴我們是優先審查還是標準審查。

All we said about it, that I recall, is, that we expect to request a priority review, which is based on our current regulatory designations with Fast Track and so forth. So that's pretty much all I know that we can say. Faye, did I leave out anything from your perspective?

我記得，我們所說的全部內容是，我們希望請求優先審查，這是基於我們目前對 Fast Track 等的監管指定。這就是我所知道的，我們可以說的差不多了。 Faye，從你的角度來看，我遺漏了什麼嗎？

Thanks, Chip. That was pretty comprehensive. I don't have anything to add.

謝謝，奇普。那是相當全面的。我沒有什麼要補充的。

Great. That's helpful. And then my other question, when you discuss the IMerge Phase III data with payers, are there any drugs that come up with comps with regards to the value that's provided to patients.

偉大的。這很有幫助。然後是我的另一個問題，當你與付款人討論 IMerge III 期數據時，是否有任何藥物在提供給患者的價值方面具有可比性。

Anil, do you want to address that?

阿尼爾，你想解決這個問題嗎？

Sure. So the question around the payer feedback is extremely positive. I think the drugs start continue to come up are obviously REBLOZYL, INQOVI, but then the lower-risk MDS landscape. But our entire discussions are focused on our value proposition both the efficacy profile, the totality of benefit and what it would mean for the payers within their value proposition. So as of right now, these discussions are extremely favorable, and this data is being received well.

當然。所以圍繞付款人反饋的問題是非常積極的。我認為開始繼續出現的藥物顯然是 REBLOZYL、INQOVI，但隨後是風險較低的 MDS 景觀。但我們的整個討論都集中在我們的價值主張上，包括功效概況、整體利益以及在他們的價值主張中對支付者意味著什麼。因此，截至目前，這些討論非常有利，並且收到的數據也很好。

Your next question comes from the line of Gil Blum with Needham.

你的下一個問題來自 Gil Blum 與 Needham 的對話。

So maybe one for Anil. How important do you think long transfusion independence data will be for effective payer coverage? And do you expect longer TIs to matter more to payers, i.e., waiting on additional IMerge data to really have a broader picture?

所以也許是給阿尼爾的。您認為長期輸血獨立性數據對於有效支付方覆蓋有多重要？您是否期望更長的 TI 對付款人更重要，即等待額外的 IMerge 數據以真正了解更廣泛的情況？

Thanks for the question. I think the durability of the TI data is extremely important, both in the U.S. as well as in Europe. This point has repeatedly come up from payers as well as clinicians to showcase the durability of TI. And the most important metric being measured from their perspective is the 24-week TI data. The fact that we have 1 year TI data on top of that, which is pretty unprecedented in this landscape, is extremely favorable to us.

謝謝你的問題。我認為 TI 數據的持久性非常重要，無論是在美國還是在歐洲。付款人和臨床醫生反复提出這一點，以展示 TI 的耐用性。從他們的角度來看，最重要的衡量指標是 24 週的 TI 數據。事實上，我們擁有 1 年的 TI 數據，這在這個領域是前所未有的，這對我們非常有利。

And in addition, the totality of benefit in terms of both reductions in transfusion burdens as well as the fact that we go across both subgroups, all of these points are being extremely well received, and we expect it to be in a very favorable position as we move forward towards launch.

此外，在減少輸血負擔以及我們跨越兩個亞組這一事實方面的總體利益，所有這些要點都非常受歡迎，我們希望它處於非常有利的位置，因為我們朝著發射前進。

Very helpful. And a quick one for Olivia. It seems like you're going to have quite significant cash burn this year. I mean, in my own calculations, I have some of your clinical study costs going away. So how do you think that this is going to be? Is this mostly OpEx going to SG&A and sales force ramp up?

很有幫助。給奧利維亞一個快速的。看起來你今年將有相當大的現金消耗。我的意思是，根據我自己的計算，我有一些臨床研究費用會減少。那麼你認為這會怎樣？這主要是用於 SG&A 和銷售人員的 OpEx 嗎？

So Gil, thanks. So it is about a $60 million increase from the '22 guidance to where we are in '23. And that is driven by a number of categories. So first, it would be headcount, and that's about 40% of the increase, regulatory submission work and everything that goes along with that for both the U.S. and the EU, that's another 10%.

吉爾，謝謝。因此，從 22 年的指導到 23 年的指導增加了約 6000 萬美元。這是由許多類別驅動的。首先，這將是員工人數，這大約佔增長的 40%，監管提交工作以及與美國和歐盟相關的一切，還有 10%。

Commercial manufacturing and building up the inventory of imetelstat, getting ready for potential commercial launch. That's another 20%. And then, in general, other activities related to commercial readiness, which is another 30%. So you want to let you know though, that overall, the clinical costs, though, still are being maintained in the company because, obviously, we have another Phase III trial going on, IMpactMF, as well as the other studies that Faye mentioned.

商業製造和建立 imetelstat 庫存，為潛在的商業發布做好準備。那是另外的 20%。然後，一般來說，與商業準備相關的其他活動，又佔 30%。所以你想讓你知道，儘管如此，總體而言，臨床成本仍在公司中維持，因為很明顯，我們正在進行另一項 III 期試驗，即 IMpactMF，以及 Faye 提到的其他研究。

This concludes our Q&A for today. I'll now turn the call back to Aron Feingold, for closing remarks.

今天的問答到此結束。我現在將電話轉回給 Aron Feingold，請他作結束語。

Thanks so much, everyone, for joining us today. We appreciate you taking the time to listen and participate. We look forward to sharing the achievement of several milestones in the coming year, stay healthy and safe everyone. Bye.

非常感謝大家今天加入我們。感謝您花時間聆聽和參與。我們期待在來年分享幾個里程碑的成就，祝大家健康平安。再見。

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

今天的電話會議到此結束。感謝您的出席。您現在可以斷開連接。