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FOSTER CITY, Calif.--(BUSINESS WIRE)--Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced presentations on RYTELO® (imetelstat) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2025 Congress. Together, the presentations reinforce the potential benefits of the first-in-class oligonucleotide telomerase inhibitor RYTELO for a range of patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia and showcase the progress Geron is making with the ongoing IMpactMF and IMproveMF trials of imetelstat in myelofibrosis (MF). “Transfusion independence is an important goal for LR-MDS patients, but one that historically has not been achievable for many,” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center. “While imetelstat is already playing a vital role in LR-MDS, these new analyses being presented at ASCO and EHA reinforce its potential to give a broad range of patients more time without transfusions and should also give clinicians confidence to add it to their toolkit as a second-line option for eligible patients.” Presentations at ASCO and EHA include: New pooled, post-hoc analyses expand on the pivotal IMerge results across challenging LR-MDS subpopulations Analysis of patients with ring sideroblast negative (RS-) disease, showing that these difficult-to-treat patients appeared to experience clinical benefit with RYTELO, including ≥8-week, ≥24-week and ≥1-year red blood cell transfusion independence (RBC-TI), duration of RBC-TI, and hemoglobin rise in patients who achieved RBC-TI, consistent with prior findings from the overall Phase 3 IMerge population. Analysis showing clinical benefit with RYTELO regardless of baseline serum erythropoietin (sEPO) level, supporting the use of RYTELO in the frontline setting for LR-MDS patients ineligible for erythropoiesis-stimulating agents (ESAs), and in the second-line setting after ESAs regardless of sEPO. Analysis showing clinical benefit with RYTELO in ESA-ineligible or relapsed/refractory patients regardless of prior treatment with luspatercept or lenalidomide. Patients who had prior treatment with a hypomethylating agent (HMA) showed modest clinical activity with RYTELO. Patient-centric outcome measures offering deeper insight on RYTELO impact in new post-hoc analyses from Phase 3 IMerge trial Analysis showing that certain RYTELO-treated patients experienced sustained improvements in health-related quality-of-life (QOL) compared with placebo, as measured by certain categories in the patient-reported QOL in Myelodysplasia Scale (QUALMS) instrument. Exploratory analysis suggesting that certain patients treated with RYTELO experienced a longer mean duration of time without transfusion reliance or relapse (TWiTR), compared with placebo. New updates on ongoing trials in MF Recently updated preliminary data from the dose escalation portion of the Phase 1/1b IMproveMF trial showing the combination of imetelstat and ruxolitinib was generally well-tolerated, with no dose-limiting toxicities observed as of the data cutoff date, and encouraging early dose-dependent efficacy data suggesting the potential of the combination for patients with intermediate-1 (INT-1), intermediate-2 (INT-2) or high-risk (HR) MF. Trial-in-progress (TiP) update on the Phase 3 IMpactMF trial investigating imetelstat in relapsed/refractory MF, reporting that the trial has met approximately 80% of its enrollment target as of February 2025. “At ASCO and EHA, we’re excited to present new analyses on how RYTELO can deliver meaningful benefit across a range of LR-MDS patients who otherwise may have had limited options, whether due to their ring sideroblast status, baseline EPO level, or their treatment history,” said Faye Feller, M.D., Executive Vice President and Chief Medical Officer of Geron. “We believe the depth and breadth of our data reinforce the potential of RYTELO to address critical unmet needs in LR-MDS and, combined with the advances we are making with our myelofibrosis program, underscore our confidence in telomerase inhibition as a potentially transformative clinical strategy and our commitment to exploring its full potential.” See below for a full schedule of presentations at ASCO and EHA. ASCO 2025 Presentations Presentation Title Author Abstract Number Presentation Details IMproveMF update: phase 1/1B trial of imetelstat (IME)+ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1, INT-2, or high-risk (HR) myelofibrosis (MF) John O. Mascarenhas, M.D. #6515 Rapid Oral, Fri. May 30, 1:00-2:30 PM CDT Effect of prior treatment (tx) on the clinical activity of imetelstat (IME) in transfusion- dependent (TD) patients (pts) with erythropoiesis-stimulating agent (ESA), relapsed or refractory (R/R)/ineligible lower-risk myelodysplastic syndromes (LR-MDS) Rami S. Komrokji, M.D. #6569 Poster, Sun. June 1, 9:00 AM-12:00 PM CDT IMpactMF, randomized, open-label, phase 3 trial of imetelstat (IME) versus best available therapy (BAT) in patients (pts) with intermediate-2 (INT-2) or high-risk (HR) myelofibrosis (MF) relapsed or refractory (R/R) to Janus kinase inhibitors (JAKi) John O. Mascarenhas, M.D. #TPS6588 Poster, Sun. June 1, 9:00 AM-12:00 PM CDT EHA 2025 Presentations Presentation Title Author Abstract Number Presentation Details Increased Duration of Time Without Transfusion Reliance (TWiTR) For Patients with LR-MDS Treated with Imetelstat Versus Placebo in the IMerge Trial Mikkael A. Sekeres, M.D. #PF646 Poster, Fri. June 13, 18:30-19:30 CEST IMproveMF Update: Phase 1/1B Trial of Imetelstat + Ruxolitinib in Patients with INT-1, INT-2, or High-Risk MF John O. Mascarenhas, M.D. #PF830 Poster, Fri. June 13, 18:30-19:30 CEST IMpactMF: Randomized, Open-Label, Phase 3 Trial of Imetelstat vs Best Available Therapy in Patients with INT-2 or High-Risk MF Relapsed/Refractory to JAK Inhibitors John O. Mascarenhas, M.D. #PF841 Poster, Fri. June 13, 18:30-19:30 CEST Health-related Quality of Life Outcomes in Patients with Lower-Risk Myelodysplastic Syndromes Treated with Imetelstat in the IMerge Trial María Díez-Campelo, M.D., Ph.D. #PS1639 Poster, Sat. June 14, 18:30-19:30 CEST Outcomes of Imetelstat Therapy in RS-Negative LR-MDS from the Pooled IMerge Study Populations Valeria Santini, M.D. #PS1622 Poster, Sat. June 14, 18:30-19:30 CEST Outcomes with Imetelstat by Serum Erythropoietin Levels in Patients with LR-MDS Who Were Treatment Naïve or Who Had Prior Treatment with Erythropoiesis-Stimulating Agents Rami S. Komrokji, M.D. #PS1640 Poster, Sat. June 14, 18:30-19:30 CEST Characterization and Management of Transient Cytopenias Associated with Imetelstat in LR-MDS from the IMerge Trial Amer M. Zeidan, M.D. #PB2760 Publication-only Please see the full presentations for important qualifications and limitations on these post-hoc analyses. About RYTELO® (imetelstat) RYTELO is an oligonucleotide telomerase inhibitor approved in the U.S. for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks. In addition, RYTELO is approved in the European Union as a monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy. RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration and the European Commission. About Geron Geron is a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer. Our first-in-class telomerase inhibitor RYTELO® (imetelstat) is approved in the United States and the European Union for the treatment of certain adult patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies. Inhibiting telomerase activity, which is increased in malignant stem and progenitor cells in the bone marrow, aims to potentially reduce proliferation and induce death of malignant cells. To learn more, visit www.geron.com or LinkedIn. US IMPORTANT SAFETY INFORMATION ABOUT RYTELO® WARNINGS AND PRECAUTIONS Thrombocytopenia RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO. Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended. Neutropenia RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO. Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended. Infusion-Related Reactions RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion. Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended. Embryo-Fetal Toxicity Based on animal findings, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose. ADVERSE REACTIONS Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%). Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at https://pi.geron.com/products/US/pi/rytelo_pi.pdf. The Summary of Product Characteristics (SmPC) for RYTELO in the EU is available at https://pi.geron.com/products/rytelo/eu/rytelo_smpc_eu.pdf Use of Forward-Looking Statements Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) that the new analyses presented at ASCO and EHA reinforce the potential benefits of RYTELO for a range of patients with LR-MDS with transfusion-dependent anemia, including its potential to give a broad range of patients more time without transfusions and should support clinician’s confidence in RYTELO as a second-line option for eligible patients; (ii) beliefs regarding imetelstat’s vital role in LR-MDS, (iii) how RYTELO can deliver meaningful benefit across a range of LR-MDS patients who otherwise may have had limited options, whether due to ring sideroblast status, baseline EPO levels, or their treatment history; (iv) Geron’s beliefs that the depth and breadth of its data reinforce the potential of RYTELO to address critical unmet needs in LR-MDS and regarding telomerase inhibition as a potentially transformative clinical strategy; and (v) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether Geron is successful in commercializing RYTELO (imetelstat) for the treatment of certain patients with LR-MDS with transfusion dependent anemia and achieves market acceptance across the breadth of the eligible patient segments in RYTELO’s approved indication; (b) whether the FDA and European Commission will approve imetelstat for other indications on the timelines expected, or at all; (c) Geron’s plans to commercialize RYTELO in the European Union, or EU and risks related to operating outside of the U.S.; (d) whether Geron overcomes potential delays and other adverse impacts that may be caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for and meet expected timelines and planned milestones; (e) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (f) whether any future safety or efficacy results of RYTELO treatment cause its benefit-risk profile to become unacceptable; (g) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (h) whether Geron meets its post-marketing requirements and commitments for RYTELO; (i) whether there are failures or delays in manufacturing or supplying sufficient quantities of RYTELO (imetelstat) or other clinical trial materials that impact commercialization of RYTELO or the continuation of its ongoing clinical trials, including the IMpactMF trial; (j) that the projected timing for the interim and final analyses of the IMpactMF trial may vary depending on actual enrollment and death rates in the trial; and (k) whether Geron stays in compliance with and satisfies its obligations under its debt and synthetic royalty financing agreements. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended March 31, 2025, and subsequent filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances.

在人体精妙的血液系统中，血小板与红细胞各司其职，维系着生命的稳态与动态平衡。前者如临阵先锋，负责止血与修复；后者则肩负着输送氧气、支撑机体代谢的重任。调控这两大细胞系生成的关键因子—血小板生成素（TPO）与促红细胞生成素（EPO），正日益成为现代精准医学干预的重要靶点。血小板生成素（TPO）TPO是一种由肝脏合成并分泌入血的信号肽，是调控巨核细胞成熟及血小板生成的主要细胞因子。在健康状态下，TPO通过负反馈机制维持血小板水平动态平衡。然而在原发免疫性血小板减少症（ITP）中，尽管血小板减少，体内TPO水平却未能显著升高，形成“相对性TPO缺乏”，为靶向TPO信号通路提供了治疗切口。近年来，以TPO受体激动剂（TPO-RA）为代表的靶向治疗快速崛起，成为ITP二线治疗主力。根据作用机制不同，TPO-RA大致分为三类：01肽类rhTPO此类代表药物为重组人血小板生成素（rhTPO），它是一种利用基因重组技术由中国仓鼠卵巢细胞表达、提纯制成的药物，它与人体自身产生的血小板生成素作用一致，起到增加血小板的作用。但长期应用rhTPO可能使患者产生内源性TPO抗体，其说明书限定使用不得超过14天。02肽类TPO-RA此类药物属于TPO肽类模拟物，是由1个IgG1 Fc载体结构域和4个高亲和力的TPO-R结合域组成的Fc融合蛋白，与内源TPO竞争相同的位点，经酪氨酸磷酸化激活多条升血小板的信号通路，促进巨核细胞增殖和分化，从而增加血小板生成，代表药物有Fc融合蛋白罗普司亭。03非肽类TPO-RA非肽类小分子药物，如艾曲泊帕、海曲泊帕和阿伐曲泊帕，能与TPO受体不同位点结合，不与内源TPO竞争，从而提供更持久的刺激。其中，艾曲泊帕是全球第一个获批上市的口服TPO-RA，由亲脂性末端、疏水性末端和金属螯合中心组成；海曲泊帕作为我国自主研发的首个口服TPO-RA，基于艾曲泊帕结构优化，疗效可靠但需空腹服用；而阿伐曲泊帕因结构特点不与金属离子螯合，可与食物同服，更具依从性优势。相关研究也证实，TPO-RA之间的序贯治疗可有效改善对前线药物无应答的患者预后。例如一项海曲泊帕治疗复发/难治性ITP的真实世界研究显示，8例由艾曲泊帕（既往治疗无应答）转换为海曲泊帕治疗的患者的应答率高达88%。EPO（促红细胞生成素）与TPO相对应，EPO（促红细胞生成素，Erythropoietin,）是另一种造血调节关键因子，分子量约30.4kDa，主要由肾脏间质细胞合成。EPO通过与红系前体细胞表面EPO受体（EPOR）结合，激活其分化增殖并促进血红蛋白合成，是慢性肾病、肿瘤相关贫血等治疗中的核心药物。早在百年前，科学家就推测血液中存在促进红细胞生成的因子。这一假设在1989年得到了实践验证，当年首款重组人促红细胞生成素（EPO）获FDA批准上市，用于治疗包括慢性肾病等引起的特定类型贫血。自此，EPO广泛应用于临床，尤其是在肿瘤合并贫血的患者中。然而，令人意想不到的是，后续研究发现，在某些癌症患者中使用EPO治疗反而加速了肿瘤生长。2007年，美国FDA为EPO类药物贴上了“黑框警告”，标示其潜在的致命风险。直到近期关于EPO与肿瘤相关巨噬细胞（TAMs）之间作用的新发现，才让这一谜题逐步揭开，并为探索全新癌症免疫治疗靶点提供了突破口。2025年4月25日，斯坦福大学Engleman团队一篇论文题目为“Tumor-derived erythropoietin acts as an immunosuppressive switch in cancer immunity”发表于《Science》杂志上，该研究以肝癌为模型，首次揭示了肿瘤细胞分泌的促红细胞生成素（Erythropoietin, EPO）作为核心调控因子，塑造了冷肿瘤的免疫抑制微环境。这项研究不仅解释了肿瘤逃逸免疫监视的关键机制，更为开发新型免疫治疗靶点开辟了全新的靶点和治疗思路。该研究团队发现，肿瘤细胞分泌的EPO通过与肿瘤相关巨噬细胞（TAMs）表面的EPO受体（EPOR）结合，形成一个免疫抑制的微环境，从而抑制T细胞的活性，使肿瘤得以逃避免疫系统的攻击。巨噬细胞中的 EPO/EPOR 信号传导具有非炎症性肿瘤免疫型吉满生物顺应市场需求与科研前沿，推出了TPO及EPO报告基因检测细胞系，并提供多种TPO相关抗体和蛋白现货产品，全面满足TPO、EPO激动剂或靶向TPO受体、EPO受体药物研发的多样化需求。所有产品均经过严格的质量检测，品质可靠。如需咨询，欢迎联系吉满生物客服（微信同号：18916119826）。临床应用方面，EPO是慢性肾病相关贫血（尤其透析患者）的首选治疗药物之一，也广泛应用于癌症患者的化疗性贫血管理。其重组版本rhEPO具有与天然EPO相似的生物活性，目前已被纳入中国医保目录。在癌性贫血治疗中，EPO能改善血红蛋白水平、提升耐受性，间接改善患者生活质量。更值得注意的是，EPO在心血管、神经保护等非造血系统中也展现出潜在治疗价值——如在缺血性心肌损伤中减少细胞凋亡，在神经发育与红细胞膜稳定性中发挥调节作用，拓展了其药理功能的边界。EPO/EPOR轴在多种实体瘤中高表达，且与预后不良密切相关，成为肿瘤免疫干预的新兴靶点。目前，全球共7款EPO药物上市，均来自海外药企，其中4款药物已在中国上市，包括阿法依泊汀（利血宝，安进）、倍他依泊汀（罗可曼，罗氏）、达依泊汀α和甲氧基聚乙二醇红细胞生成素（美信罗，罗氏）。2024年9月3日，CDE网站显示，步长制药的艾帕依泊汀α（rhEPO-Fc）申报上市，用于治疗慢性肾病贫血。艾帕依泊汀α是步长制药开发的一款促红细胞生成素-Fc（EPO-Fc）融合蛋白，属于长效EPO药物。总结从基础造血调节因子，到精准免疫治疗靶点，TPO与EPO的“双主角”角色正在被重新定义。它们不仅在出血和贫血性疾病治疗中发挥核心作用，更揭示了肿瘤微环境调控、免疫逃逸机制等更深层的生物学奥秘。未来，随着靶向结构优化、生物标志物开发和递送技术提升，TPO与EPO类药物有望拓展至更广泛的疾病谱系，为临床治疗带来更精准、高效的干预策略。而EPO/EPOR轴，或正开启一场从造血调节到免疫重塑的治疗革命。吉满生物吉满生物推出构建STEAP系列（STEAP1、STEAP2、STEAP3、STEAP4）稳定过表达细胞系/抗体的服务，充分满足药物研发需求，助力药物临床申报。产品列表数据展示GM-C30062 H_TPO Reporter 293 Cell Line使用Human TPO Protein; His Tag激活验证结果GM-C33026 H_EPO Reporter 293 Cell Line使用Recombinant Human EPO (C-6His)激活验证结果联系我们吉满生物(Genomeditech)成立于2011年，是专业从事生物科技服务和前沿技术研发的高新技术企业。吉满生物专注为生物药开发赋能，自主创立了国内知名的细胞系品牌-DDXCELL，目前已布局近400个热门靶向药靶点，超1000株现货单克隆细胞系，涵盖GPCR、细胞因子、免疫检查点、TAA等多领域，做到进口细胞的国产替代。此外，吉满生物还可在药物研发进程中提供一系列抗体、蛋白产品，旨在为客户提供高效的研发工具和解决方案!扫码咨询扫码找现货