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 the publication of abstracts containing new data highlighting the potential of RYTELO™ (imetelstat), a first-in-class telomerase inhibitor, in myeloid hematologic malignancies.

加利福尼亚州福斯特城（商业新闻短讯）--Geron Corporation（Nasdaq:GERN）是一家商业阶段的生物制药公司，旨在通过改变血癌的进程来改变生活，今天宣布发表摘要，其中包含新数据，突出了一流端粒酶抑制剂RYTELO™（imetelstat）在髓系血液系统恶性肿瘤中的潜力。

Six abstracts have been accepted for presentation at the 66th American Society of Hematology (ASH) Annual Meeting taking place from December 7-10, 2024, in San Diego, California and virtually..

六篇摘要已被接受在2024年12月7日至10日在加利福尼亚州圣地亚哥举行的第66届美国血液学会（ASH）年会上发表。。

“We look forward to collaborating with our trial investigators to present meaningful data updates across the imetelstat pipeline, which we believe continue to highlight telomerase inhibition as an important and powerful approach to treating myeloid hematologic malignancies,” said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron..

“我们期待着与我们的试验研究人员合作，在imetelstat管道中提供有意义的数据更新，我们相信这将继续突出端粒酶抑制作为治疗骨髓恶性血液病的重要而有力的方法，”Geron执行副总裁兼首席医官Faye Feller医学博士说。。

Lower-Risk Myelodysplastic Syndromes (LR-MDS)

低风险骨髓增生异常综合征（LR-MDS）

Abstract #352: “Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes”

摘要#352：“先前治疗对输血依赖的红细胞生成刺激剂，复发或难治性/不合格的低风险骨髓增生异常综合征患者的依替司他临床活性的影响”

Oral presentation on Saturday, December 7, 2024 at 4:45 p.m. PT by Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig University Hospital, Leipzig, Germany

2024年12月7日星期六下午4:45由德国莱比锡莱比锡大学医院血液学、细胞疗法、止血学和传染病系医学博士Uwe Platzbecker进行口头介绍

This abstract evaluates the effect of prior treatments on the clinical activity of imetelstat in patients with red blood cell (RBC) transfusion-dependent (TD) LR-MDS in an analysis of imetelstat-treated patients pooled from the IMerge Phase 2, Phase 3 and QTc studies (N=226). The results suggest that imetelstat demonstrates RBC-transfusion-related clinical activity and increases in hemoglobin in these patients regardless of prior therapies, although there are limited data on outcomes in later lines of treatment..

本摘要评估了先前治疗对红细胞（RBC）输血依赖性（TD）LR-MDS患者依美司他临床活性的影响，分析了依美司他治疗的患者，这些患者来自IMerge 2期，3期和QTc研究（N=226）。结果表明，imetelstat在这些患者中表现出与红细胞输注相关的临床活性和血红蛋白的增加，无论之前的治疗方法如何，尽管后期治疗的结果数据有限。。

“There are very few treatment options today for patients with lower-risk MDS who have symptomatic anemia and are transfusion dependent, which often results in patients having to cycle through available therapies. By pooling data across the IMerge clinical trial, we sought to understand the potential of treatment with imetelstat for these patients regardless of their prior treatment.

“对于有症状性贫血且依赖输血的低风险MDS患者，目前几乎没有治疗选择，这通常导致患者不得不循环使用可用的治疗方法。通过汇总IMerge临床试验的数据，我们试图了解使用imetelstat治疗这些患者的潜力，无论他们之前的治疗如何。

Although we have small numbers in some cases, these data have important clinical implications, suggesting that these patients experienced a RBC-transfusion related clinical benefit and improvements in hemoglobin with imetelstat regardless of their prior treatment,” said Dr. Platzbecker..

Platzbecker博士说：“尽管在某些情况下我们的数字很少，但这些数据具有重要的临床意义，表明这些患者无论之前接受过何种治疗，都经历了与红细胞输注相关的临床益处，并且使用imetelstat改善了血红蛋白。”。。

Therapy received prior to imetelstat treatment*

在imetelstat治疗之前接受的治疗*

≥8-week RBC-TI

≥8周RBC-TI

≥24-week RBC-TI

≥24周RBC-TI

RBC Transfusion Reduction of ≥4 U/8 weeks

红细胞输血减少≥4 U/8周

Hb Rise of ≥1.5 g/dL for ≥8 weeks

Hb升高≥1.5 g/dL，持续≥8周

HI-E (IWG 2018)

HI-E（IWG 2018）

ESA (n=204)

欧空局（n=204）

40%

40%

28%

28%

64%

64%

33%

33%

43%

43%

Luspatercept (n=35)

Luspatercept（n=35）

29%

29%

20%

20%

69%

69%

29%

29%

26%

26%

Lenalidomide (n=26)

来那度胺（N=26）

23%

23%

12%

12%

54%

54%

19%

19%

31%

31%

HMA (n=22)

HMA（n=22）

14%

14%

9%

9%

50%

50%

14%

14%

18%

18%

*Prior treatment was not mutually exclusive; patients may have received more than one prior therapy.

*先前的治疗并不是相互排斥的；患者可能接受过不止一次治疗。

RBC-TI, red blood cell-transfusion independence; HI-E, hematologic improvement-erythroid; IWG, International Working Group; Hb, hemoglobin; ESA, erythropoiesis-stimulating agent; HMA, hypomethylating agent.

RBC-TI，红细胞输血独立性；HI-E，血液学改善红细胞；IWG，国际工作组；血红蛋白，血红蛋白；ESA，红细胞生成刺激剂；HMA，低甲基化剂。

Additionally, in imetelstat-treated patients ineligible for ESA therapy (n=22) treated in the front-line, 36% and 14% achieved ≥8-week and ≥24-week RBC-TI, respectively, 41% met HI-E, 64% had a transfusion reduction of ≥4 U/8 weeks, and 2% had a Hb rise of ≥1.5 g/dL for ≥8 weeks.

此外，在不符合ESA治疗资格（n=22）的一线治疗患者中，36%和14%分别达到≥8周和≥24周RBC-TI，41%达到HI-E，64%输血减少≥4 U/8周，2%血红蛋白升高≥1.5 g/dL≥8周。

Abstract #4590: “Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents”.

摘要#4590：“IMerge 3期试验的QTc亚组研究的初步结果表明，对于接受过红细胞生成刺激剂以外的先前治疗的低风险骨髓增生异常综合征患者，临床上有意义的疗效，可控的安全性以及无致心律失常风险”。

Poster presentation on Monday, December 9, 2024 from 6:00 p.m. - 8 p.m. PT by Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center

2024年12月9日（星期一）下午6:00至8:00由医学博士Rami S.Komrokji（莫菲特癌症中心恶性血液科副主席）发布海报

This abstract reports the first efficacy and safety results from the ventricular repolarization IMerge QTc substudy conducted per FDA guidance. This substudy differed from the IMerge Phase 3 trial in its crossover design, by allowing prior lenalidomide and HMA therapy besides ESAs and by allowing lower-risk MDS patients with the del(5q) mutation.

本摘要报告了根据FDA指南进行的心室复极IMerge QTc亚研究的首次疗效和安全性结果。该亚研究在交叉设计上不同于IMerge 3期试验，除了ESA外，还允许先前的来那度胺和HMA治疗，并且允许具有del（5q）突变的低风险MDS患者。

As of the data cutoff on May 10, 2024, no clinically meaningful effects of imetelstat on cardiac repolarization or other ECG parameters were observed. In the 51 total imetelstat-treated patients (35 randomized and 16 crossover), the median treatment duration was 29.3 weeks and the median (95% CI) duration of RBC-TI among ≥8-week RBC-TI responders was 52.6 weeks (40.9-non estimable).

截至2024年5月10日的数据截止，未观察到imetelstat对心脏复极或其他ECG参数的临床意义。在51例接受imetelstat治疗的患者中（35例随机，16例交叉），中位治疗时间为29.3周，≥8周RBC-TI反应者的RBC-TI中位（95%CI）持续时间为52.6周（40.9-不可估计）。

Subgroup analyses showed ≥8-week RBC-TI rates of 30% (7/23) and 50% (14/28) in patients with and without prior luspatercept, 38% (5/13) and 42% (16/38) in patients with and without prior lenalidomide, and 21% (3/14) and 49% (18/37) in patients with and without prior HMA use, respectively. No new safety signals emerged, and in the total imetelstat-treated population, Grade 3/4 neutropenia and thrombocytopenia by laboratory evaluation occurred in 65% (33/51) and 49% (25/51) of patients, respectively, of which most cases resolved to Grade ≤2 within four weeks; incidence was similar to the overall Phase 3 imetelstat-treated population.

亚组分析显示，既往有无luspatercept的患者≥8周RBC-TI率分别为30%（7/23）和50%（14/28），38%（5/13）和42%（16/38）有和没有来那度胺的患者，以及21%（3/14）和49%（18/37）有和没有使用HMA的患者。没有出现新的安全性信号，在imetelstat治疗的总人群中，实验室评估的3/4级中性粒细胞减少症和血小板减少症分别发生在65%（33/51）和49%（25/51）的患者中，其中大多数病例在四周内达到≤2级；发病率与整体3期imetelstat治疗人群相似。

In this QTc substudy, efficacy and safety of imetelstat were comparable to that shown in the overall population of the IMerge Phase 3 trial, and notably, responses to imetelstat were seen in patients receiving prior treatments including luspatercept, lenalidomide, and HMAs..

在这项QTc亚研究中，imetelstat的疗效和安全性与IMerge 3期临床试验的总体人群相当，值得注意的是，在接受luspatercept，来那度胺和HMAs等先前治疗的患者中观察到了对imetelstat的反应。。

Abstract #3210: “Correlation of Patient-Reported Outcomes with Red Blood Cell Transfusion Reduction and Rise in Hemoglobin in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Trial”

摘要#3210：“IMerge试验中低风险骨髓增生异常综合征患者报告的结果与红细胞输血减少和血红蛋白升高的相关性”

Poster presentation on Sunday, December 8, 2024 from 6:00 p.m. - 8 p.m. PT by Mikkael Sekeres, MD, University of Miami Health System and Sylvester Comprehensive Cancer Center

2024年12月8日星期日下午6:00至8:00由迈阿密大学卫生系统和西尔维斯特综合癌症中心医学博士Mikkael Sekeres发布海报

This abstract reports on post-hoc analyses of the patient-reported outcome (PRO) population from the IMerge Phase 3 clinical trial (N=175; 118 treated with imetelstat and 57 treated with placebo). PROs were assessed with validated Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Functional Assessment of Cancer Therapy-Anemia (FACT-An), and the Quality of Life in Myelodysplasia Scale (QUALMS) questionnaires.

该摘要报告了来自IMerge 3期临床试验（N=175；118例用imetelstat治疗，57例用安慰剂治疗）的患者报告结果（PRO）人群的事后分析。PRO通过验证的慢性病治疗功能评估（FACIT）-疲劳，癌症治疗贫血功能评估（FACT-An）和骨髓增生异常症生活质量量表（QUALMS）问卷进行评估。

In the ring sideroblast positive (RS+) and RS negative (RS-) groups, respectively, sustained, meaningful improvement in fatigue was achieved by 55% and 43% of imetelstat-treated patients; differences (95% CI) versus placebo appeared to favor imetelstat (9% [−12, 29] for RS+ and 13% [−15, 36] for RS−).

在环铁粒幼细胞阳性（RS+）和RS阴性（RS-）组中，分别有55%和43%的imetelstat治疗患者获得了持续的，有意义的疲劳改善；与安慰剂相比，差异（95%可信区间）似乎有利于imetelstat（RS+为9%[-12,29]，RS-为13%[-15,36]）。

Similarly, in patients with prior transfusion burdens of 4-6 U/8 weeks or >6 U/8 weeks, respectively, sustained improvement in fatigue was achieved by 44% and 57% of imetelstat-treated patients; differences (95% CI) versus placebo appeared to favor imetelstat (8% [−15, 29] for 4-6 U/8 weeks and 11% [−13, 34] for >6 U/8 weeks).

同样，在先前输血负担分别为4-6 U/8周或>6 U/8周的患者中，44%和57%的imetelstat治疗患者的疲劳持续改善；。

Similar to the RBC-TI response and improvement in fatigue association, for imetelstat-treated patients with versus in those without a ≥1.5-g/dL increase in hemoglobin lasting ≥8 weeks, improvements in fatigue were seen in 70% (28/40) versus 40% of patients, respectively (31/78; nominal P-value=.003); in those with versus in those without transfusion reduction of ≥4 U/8 weeks, improvements were seen in 69% (49/71) versus 21% of patients (10/47; nominal P-value <.001).

与RBC-TI反应和疲劳相关性改善类似，对于依替司他治疗的血红蛋白持续≥8周≥1.5-g/dL的患者与未持续≥8周的患者相比，疲劳改善率分别为70%（28/40）和40%（31/78；标称P值=0.003）；输血减少≥4 U/8周的患者与未输血减少≥4 U/8周的患者相比，69%（49/71）的患者有所改善，而21%的患者（10/47；标称P值<0.001）。

The QUALMS and FACT-An analyses suggested that imetelstat maintained QOL and anemia symptoms, while placebo recipients experienced worsening QOL and anemia symptoms..

疑虑和事实分析表明，imetelstat维持了生活质量和贫血症状，而安慰剂接受者的生活质量和贫血症状恶化。。

“Low quality of life can be one of the most devastating and burdensome impacts of living with lower-risk MDS, particularly when patients are anemic and transfusion-dependent. The sustained improvement in fatigue and maintenance of quality of life and anemia symptoms with imetelstat shown in these post-hoc analyses are meaningful and very encouraging as we aim to improve outcomes for these patients,” Dr.

“低生活质量可能是低风险MDS患者生活中最具破坏性和负担最重的影响之一，特别是当患者贫血和依赖输血时。这些事后分析显示，依替司他持续改善疲劳，维持生活质量和贫血症状是有意义的，非常令人鼓舞，因为我们的目标是改善这些患者的预后，”Dr。

Platzbecker continued..

Platzbecker继续说道。。

Myelofibrosis (MF)

Abstract #998: “Trial Update from IMproveMF, an Ongoing, Open-Label, Dose-Escalation and -Expansion, Phase 1/1B Trial to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Novel Combination of Imetelstat with Ruxolitinib in Patients with Intermediate-1, Intermediate-2, or High-Risk Myelofibrosis (MF)”.

摘要#998：“IMPROVEEMF的试验更新，这是一项正在进行的，开放标签，剂量递增和扩大的1/1B期试验，用于评估Imetelstat与Ruxolitinib新型组合在中度1，中度2或高危骨髓纤维化（MF）患者中的安全性，药代动力学和临床活性”。

Oral presentation on Monday, December 9, 2024 at 4:45 p.m. PT by John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mount Sinai

2024年12月9日星期一下午4:45由西奈山伊坎医学院医学博士约翰·马斯卡伦哈斯（JohnMascarenhas）在PT进行口头介绍

This abstract reports the first safety results from the dose escalation Part 1 of the Phase 1/1B IMproveMF clinical trial, in which 13 patients were enrolled as of July 10, 2024. At least three patients received each dose level of imetelstat and doses of ruxolitinib were individualized per patient. No dose limiting toxicities (DLTs) were observed, and adverse events were consistent with those observed in other clinical trials of imetelstat.

该摘要报告了1/1B期IMproveMF临床试验剂量递增第1部分的第一个安全性结果，截至2024年7月10日，共有13名患者入选。。没有观察到剂量限制性毒性（DLT），不良事件与imetelstat其他临床试验中观察到的一致。

Imetelstat and ruxolitinib pharmacokinetic profiles in the combination study were similar to previous monotherapy studies. These early results show potential for the tolerability of the combination of imetelstat and ruxolitinib in this frontline MF patient population..

联合研究中的Imetelstat和ruxolitinib药代动力学特征与之前的单一疗法研究相似。。。

“These early results support the potential tolerability of imetelstat as a combination therapy and could have significant implications for future development efforts,” continued Dr. Feller.

“这些早期结果支持了imetelstat作为联合疗法的潜在耐受性，并可能对未来的开发工作产生重大影响，”Feller博士继续说道。

Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)

急性髓细胞白血病（AML）和高危骨髓增生异常综合征（HR-MDS）

Abstract #3222: “A Phase II Study Evaluating the Efficacy and Safety of Imetelstat in Patients with Advanced Myelodysplastic Neoplasms or AML Failing HMA-Based Therapy - Interim Analysis Results of the IMpress Study”

摘要#3222：“一项II期研究，评估依替司他对晚期骨髓增生异常肿瘤或AML失败的HMA治疗患者的疗效和安全性-IMpress研究的中期分析结果”

Poster presentation on Sunday, December 8, 2024 from 6:00 p.m. - 8 p.m. PT by Uwe Platzbecker, M.D.

2024年12月8日星期日下午6:00-8:00由医学博士Uwe Platzbecker发布海报。

This abstract, submitted by Geron collaborators, provides an interim analysis from the Phase 2 IMpress trial, led by the European Myelodysplastic Neoplasms Cooperative Group (EMSCO), which is evaluating imetelstat in patients with HR-MDS or AML, refractory, relapsing or intolerant to either azacitidine or decitabine, or venetoclax plus azacitidine.

这份由Geron合作者提交的摘要提供了由欧洲骨髓增生异常肿瘤合作组织（EMSCO）领导的2期IMpress试验的中期分析，该试验正在评估imetelstat治疗HR-MDS或AML患者，难治性，复发性或不耐受阿扎胞苷或地西他滨，或venetoclax加阿扎胞苷。

Between June and October 2023, 23 patients (6 HR-MDS, 17 AML) received at least one dose of imetelstat with an average of 2.8 doses administered per patient. In this first part of the trial, none of the 23 treated patients reached the primary endpoint visit, which was scheduled after 4 cycles of treatment.

2023年6月至10月，23名患者（6名HR-MDS，17名AML）接受了至少一剂imetelstat，每位患者平均服用2.8剂。在试验的第一部分，23名接受治疗的患者均未达到主要终点访视，该访视计划在4个治疗周期后进行。

Sixteen of these 23 patients reached the preliminary disease assessment visit after two cycles of imetelstat; one patient showed a response in hematologic improvements in the erythroid and platelet lineages (HI-E and HI-P), 7 patients had stable disease and 8 patients had progressive disease. Short-term transient improvement in hematological values was observed in individual cases.

这23名患者中有16名在两个周期的imetelstat治疗后达到了初步的疾病评估访视；一名患者在红细胞和血小板谱系（HI-E和HI-P）的血液学改善方面表现出反应，7名患者病情稳定，8名患者病情进展。在个别病例中观察到血液学值的短期短暂改善。

In patients on the LR-MDS dosing schedule of every four weeks, imetelstat showed some antiproliferative effects, including a decline in blasts and leukocytes. Overall, no new safety signals occurred beyond those already known for imetelstat. A total of 30 serious adverse events (SAEs) occurred in 18 patients of which 21 SAEs required hospitalizations.

在每四周LR-MDS给药方案的患者中，imetelstat显示出一些抗增殖作用，包括母细胞和白细胞的下降。总体而言，除了imetelstat已知的安全信号之外，没有出现新的安全信号。18例患者共发生30例严重不良事件（SAE），其中21例SAE需要住院治疗。

Based on the observations in this first cohort, the protocol was amended to a more frequent dosing schedule for a second cohort of patients being enrolled and treated with this modified schedule starting in August 2024..

根据第一组患者的观察结果，从2024年8月开始，该方案被修改为第二组患者更频繁的给药时间表，并从该修改后的时间表开始接受治疗。。

Abstract #52: “Overcoming Ven/Aza Resistance Through Imetelstat-Mediated Lipophagy in Acute Myeloid Leukemia”

摘要#52：“通过Imetelstat介导的脂质自噬克服急性髓细胞白血病的Ven/Aza耐药性”

Oral presentation on Saturday, December 7, 2024 at 10:15 a.m. PT by Claudia Bruedigam, Team Head, Leukaemia Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia

澳大利亚昆士兰QIMR Berghofer医学研究所白血病代谢实验室团队负责人Claudia Bruedigam于2024年12月7日星期六上午10:15进行口头介绍

This abstract, submitted by Geron collaborators, shares pre-clinical data identifying imetelstat-mediated, ferroptosis-associated lipidomic alterations in AML cells that correlate with imetelstat treatment responses in vivo. These mechanistic insights may be leveraged to develop an optimized therapeutic strategy using imetelstat to target venetoclax/azacitidine resistant AML subclones..

这份由Geron合作者提交的摘要共享了临床前数据，这些数据确定了与体内依替司他治疗反应相关的AML细胞中依替司他介导的，与铁浓化相关的脂质组学改变。这些机制的见解可用于开发使用imetelstat靶向venetoclax/阿扎胞苷耐药AML亚克隆的优化治疗策略。。

About RYTELO™ (imetelstat)

关于RYTELO™（imetelstat）

RYTELO™ (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor 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).

RYTELO™（imetelstat）是一种FDA批准的寡核苷酸端粒酶抑制剂，用于治疗患有输血依赖性贫血的低至中1风险骨髓增生异常综合征（LR-MDS）的成年患者，需要四个或更多红细胞单位超过八周，对红细胞生成刺激剂（ESA）没有反应或失去反应或不合格。

It is indicated to be administered as an intravenous infusion over two hours every four weeks..

它被指示每四周静脉输注两小时以上。。

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.

RYTELO是一种通过抑制端粒酶酶活性起作用的一流治疗方法。端粒是染色体末端的保护帽，每次细胞分裂时都会自然缩短。在LR-MDS中，异常的骨髓细胞通常表达端粒酶，端粒酶可以重建这些端粒，从而使细胞分裂不受控制。

Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration..

RYTELO由Geron开发并独家拥有，是美国食品和药物管理局批准的第一种也是唯一一种端粒酶抑制剂。。

IMPORTANT SAFETY INFORMATION

重要安全信息

WARNINGS AND PRECAUTIONS

警告和注意事项

Thrombocytopenia

血小板减少症

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.

根据实验室值，RYTELO可引起血小板减少症。。

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..

监测血小板减少症患者的出血情况。在RYTELO开始之前，每周监测前两个周期的全血细胞计数，之后的每个周期之前以及临床指示。酌情进行血小板输注。延迟下一个周期并以相同或减少的剂量恢复，或根据建议停止。。

Neutropenia

中性粒细胞减少

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.

根据实验室值，RYTELO可引起中性粒细胞减少症。在临床试验中，72%接受RYTELO治疗的MDS患者出现新的或恶化的3级或4级中性粒细胞减少。

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.

监测3级或4级中性粒细胞减少症患者的感染，包括败血症。在RYTELO开始之前，每周监测前两个周期的全血细胞计数，之后的每个周期之前以及临床指示。酌情使用生长因子和抗感染疗法进行治疗或预防。

Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended..

延迟下一个周期并以相同或减少的剂量恢复，或根据建议停止。。

Infusion-Related Reactions

输液相关反应

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%).

RYTELO可引起输液相关反应。在临床试验中，用RYTELO治疗的MDS患者中有8%发生了输注相关反应；3级或4级输液相关反应发生率为1.7%，包括高血压危象（0.8%）。最常见的输液相关反应是头痛（4.2%）。

Infusion-related reactions usually occur during or shortly after the end of the infusion..

输注相关反应通常发生在输注期间或输注结束后不久。。

Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for 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..

根据建议，在输注苯海拉明和氢化可的松之前至少30分钟对患者进行术前用药，并根据建议在输注后监测患者1小时。通过支持治疗和输液中断来管理输液相关反应的症状，降低输液速度，或根据建议永久停止输液。。

Embryo-Fetal Toxicity

胚胎-胎儿毒性

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.

RYTELO给孕妇服用时会导致胚胎-胎儿损伤。告知孕妇对胎儿的潜在风险。建议有生殖潜力的女性在使用RYTELO治疗期间和最后一剂后1周内使用有效的避孕措施。

ADVERSE REACTIONS

不良反应

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%)..

接受RYTELO治疗的患者中有32%发生严重不良反应。>2%的患者出现严重不良反应，包括败血症（4.2%）和骨折（3.4%），心力衰竭（2.5%）和出血（2.5%）。接受RYTELO治疗的患者中有0.8%发生致命的不良反应，包括败血症（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..

包括实验室异常在内的最常见不良反应（≥10%，与安慰剂组相比差异>5%）是血小板减少，白细胞减少，中性粒细胞减少，AST升高，碱性磷酸酶升高，ALT升高，疲劳，部分凝血活酶时间延长，关节痛/肌痛，COVID-19感染和头痛。。

Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at https://pi.geron.com/products/US/pi/rytelo_pi.pdf.

https://pi.geron.com/products/US/pi/rytelo_pi.pdf.

About Geron

关于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 for the treatment of certain adult patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia.

Geron是一家商业化阶段的生物制药公司，旨在通过改变血癌的病程来改变生活。我们的一流端粒酶抑制剂RYTELO™（imetelstat）在美国被批准用于治疗某些患有输血依赖性贫血的低风险骨髓增生异常综合征（LR-MDS）的成年患者。

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.

我们还正在进行imetelstat在JAK抑制剂复发/难治性骨髓纤维化（R/R MF）中的关键3期临床试验，以及其他血液系统恶性肿瘤的研究。抑制端粒酶活性，其在骨髓中的恶性干细胞和祖细胞中增加，旨在潜在地减少增殖并诱导恶性细胞死亡。

To learn more, visit www.geron.com or follow us on LinkedIn..

要了解更多信息，请访问www.geron.com或在LinkedIn上关注我们。。

Use of Forward-Looking Statements

前瞻性声明的使用

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) Geron’s plans to collaborate with trial investigators across the imetelstat pipeline and its belief in telomerase inhibition as an important and powerful approach to treating myeloid hematologic malignancies; (ii) results from an analysis of imetelstat-treated patients pooled from the IMerge Phase 2, Phase 3 and QTc studies that suggests that patients with lower-risk MDS who have symptomatic anemia and are transfusion dependent experience a clinical benefit with imetelstat regardless of their prior treatment; (iii) observation of sustained improvement in fatigue and maintenance of quality of life and anemia symptoms with imetelstat shown in post-hoc analyses that are meaningful and encouraging; (iv) the potential tolerability of imetelstat as a combination therapy; and (v) other statements that are not historical facts, constitute forward-looking statements.

除了本文包含的历史信息外，本新闻稿还包含根据1995年《私人证券诉讼改革法》的“安全港”规定所作的前瞻性声明。投资者应注意，此类声明包括但不限于以下内容：（i）Geron计划与imetelstat管道的试验研究人员合作，并相信端粒酶抑制是治疗髓系血液系统恶性肿瘤的重要而有力的方法；（ii）从IMerge 2期，3期和QTc研究中汇总的imetelstat治疗患者的分析结果表明，患有症状性贫血且依赖输血的低风险MDS患者无论之前的治疗如何，都能从imetelstat获得临床益处；（iii）在事后分析中观察到imetelstat持续改善疲劳和维持生活质量和贫血症状，这是有意义和令人鼓舞的；（iv）imetelstat作为联合治疗的潜在耐受性；（v）其他非历史事实的陈述，构成前瞻性陈述。

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; (b) whether Geron overcomes potential delays and other adverse impacts caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challeng.

这些前瞻性陈述涉及风险和不确定性，可能导致实际结果与此类前瞻性陈述中的结果存在重大差异。这些风险和不确定性包括但不限于与以下相关的风险和不确定性：（a）Geron是否成功地将RYTELO（imetelstat）商业化，用于治疗某些患有输血依赖性贫血的LR-MDS患者；（b） Geron是否克服了入学、临床、安全、有效性、技术、科学、知识产权、制造和监管挑战带来的潜在延误和其他不利影响。