Erythropoietin(Xiamen Amoytop Biotech Co. Ltd.)

摘要 PIIF 智造创新 文章梳理了以中心法则理论为基础，重组人胰岛素、重组人促红细胞生成素、单克隆抗体等里程碑药物的研发演进轨迹；概述了主要表达系统、高密度发酵和纯化工艺等共性技术。鉴于正确折叠（复性）是重组蛋白药物研发的最大难点之一，本文追溯了蛋白折叠领域的发展历程，重点归纳了折叠中间体理论，尤其是二硫键在折叠动力学中的双重作用：既能锁定蛋白的天然态，也能诱导折叠中间体陷入动力学陷阱，为工业化复性重组蛋白药物（如重组人血管内皮抑制素）提供了理论依据。 一 重组蛋白药物研发概述 自20 世纪70 年代重组脱氧核糖核酸（deoxyribonucleic acid，DNA）技术问世以来，医药产业经历了从“化学小分子”向“生物大分子”的深刻变革。半个世纪间，重组蛋白药物不仅重塑了肿瘤、自身免疫及代谢性疾病的治疗范式，更驱动了分子生物学、计算生物学与结构表征技术的跨越式演进。鉴于该领域五十载进程之宏大，本文无意提供全覆盖的文献汇编，而是着眼于勾勒行业演进的核心脉络与关键转折。在文献引用上，本文重点关注开创性成果及支撑技术逻辑演进的代表性研究；受限于篇幅，未能尽录其他同行优秀贡献，文中难免有所疏漏，尚祈见谅。 二 中心法则与重组蛋白 药物研发 二十世纪中叶的一系列关键发现，共同奠定了重组DNA 技术的理论基础。1944 年，美国科学家Oswald Avery，Colin MacLeod 和Maclyn McCarty 的实验证明了DNA 是遗传信息的载体[1]。1953 年4 月，James Watson 和Francis Crick 阐明了DNA 双螺旋结构，两人因此获得了1962 年诺贝尔生理学或医学奖[2]。在此基础上，Francis Crick 于1958 年提出“中心法则”（central dogma），阐明了遗传信息从DNA 到核糖核酸（ribonucleic acid，RNA）再到蛋白质的流动方向[3]。 1961 年，Christian B. Anfinsen 等人通过对核糖核酸酶（ribonuclease，RNase）的变性与复性实验，首次提出了蛋白的一级序列包含了决定其三级结构的全部信息[4]。这一原始发现确立了蛋白质折叠（protein folding）热力学假说的底层逻辑[5]，Anfinsen 也因此获得了1972 年诺贝尔化学奖。 三 重组蛋白药物的 基本概念与分类 重组蛋白药物是指通过DNA 重组技术，在工程化的宿主系统中生产得到的具有明确治疗功能的蛋白或多肽，具备高特异性、低脱靶毒性等特征[12]。主要分为6 类：①多肽与重组激素类，如人胰岛素、生长激素。②细胞因子类，如干扰素、促红细胞生成素（erythropoietin，EPO）。③重组血液制品、重组酶与凝血因子，如组织型纤溶酶原激活剂[13]、重组人血清白蛋白（recombinant human serum albumin，rHSA）。④单克隆抗体及衍生物，如1984 年诞生的嵌合抗体[14]。⑤重组融合蛋白，如“免疫黏附素（immunoadhesins）”[15]。⑥修饰型重组蛋白，如聚乙二醇化技术[16]。 NEWS 欢迎扫码关注我们 版权说明：本文来源于“中国食品药品监管杂志”，由“PIIF智造创新”平台综合整理发布，版权归原作者所有，转载请注明出处。

Investigator-sponsored study, conducted at the Moffitt Cancer Center, demonstrates safety and efficacy consistent with the Phase 3 IMerge trial in a broader patient population Additional presentations at EHA 2026 and ASCO 2026 include abstracts related to ongoing myelofibrosis and AML clinical programs FOSTER CITY, Calif., May 12, 2026 (GLOBE NEWSWIRE) -- Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced that the first real-world evidence study of RYTELO® (imetelstat) in patients with lower-risk myelodysplastic syndromes (LR-MDS) will be presented at the European Hematology Association (EHA) 2026 Congress. The retrospective and prospective investigator-sponsored study, conducted at the Moffitt Cancer Center, reported safety and clinical efficacy of imetelstat in advanced, heavily transfusion dependent patients with LR-MDS, including patients with extensive prior therapies and after luspatercept failure. Data from the retrospective portion of the study will be presented at the EHA 2026 Congress. “Imetelstat has become an important treatment option for patients with lower-risk myelodysplastic syndromes experiencing anemia and red blood cell transfusion burden, particularly in patients previously treated with ESAs or other therapies,” said David A. Sallman, M.D., Associate Member, Malignant Hematology Department, Moffitt Cancer Center. “As treatment sequencing has emerged as an increasing area of focus in LR-MDS, real-world analyses such as this study can help provide additional context on how therapies are being used in routine clinical practice and across more diverse patient populations. We look forward to presenting these data at EHA 2026.” “This is the first real-world study evaluating imetelstat in lower-risk MDS, and we are encouraged that the efficacy, safety and tolerability observed were generally consistent with findings from the Phase 3 IMerge trial in a broader patient population with a trend towards more optimal management of cytopenias,” said Joseph E. Eid, M.D., Executive Vice President, Research and Development and Chief Medical Officer of Geron. “These findings add to the growing body of evidence supporting the use of imetelstat as a preferred treatment option following prior therapy for patients with lower-risk MDS and significant transfusion burden. We look forward to presenting data from the prospective portion of this study later this year.” The data, from the retrospective portion of the investigator-sponsored study, evaluated imetelstat in 40 patients with lower-risk MDS treated at the Moffitt Cancer Center in a real-world setting following U.S. Food and Drug Administration (FDA) approval. Patients included in the analysis had advanced, heavily transfusion-dependent disease and extensive prior treatment exposure, including prior luspatercept, erythropoiesis-stimulating agents (ESAs), hypomethylating agents and lenalidomide. With 14-month follow-up, the analysis reported a red blood cell (RBC) transfusion independence rate of 37.5% lasting at least eight weeks (RBC-TI > 8 weeks) with several responses ongoing at the time of analysis and identified potential predictors of response. The safety profile observed in the study was generally consistent with the known safety profile of imetelstat. Cytopenias were reported as the most common Grade 3/4 adverse event. Exploratory analyses also suggested a trend toward improved responses when imetelstat was used within the first three lines of therapy. Geron will also have additional presentations at the EHA 2026 Congress and the American Society of Clinical Oncology (ASCO) 2026 Annual Meeting, including abstracts related to its ongoing myelofibrosis clinical programs. This includes an updated overall survival analysis in patients with myelofibrosis treated with imetelstat in the Phase 2 IMbark trial compared with real-world data. Additional Presentations EHA and ASCO include:EHA 2026 Presentations Presentation TitleAuthorAbstract NumberPresentation DetailsReal-world Outcomes of Imetelstat: Interrogating Safety, Efficacy and Predictors of Response in Heavily Pretreated Lower-Risk MDS Patients*David A. Sallman, M.D.#PF670Poster, Jun 12, 18:45-19:45 CESTUpdated Analysis of Overall Survival with Imetelstat in Patients with Relapsed or Refractory Myelofibrosis From IMBark Versus Real-world Data, and Assessment of Real-world Treatment PatternsAndrew T. Kuykendall, M.D.#PB3419Publication-onlyPhase 1/1B Trial of Imetelstat and Azacitadine with or without Venetoclax in Relapsed Acute Myeloid Leukemia (IMAGINE Trial)*Douglas A. Tremblay, M.D.#PB2719Publication-only *Investigator-sponsored Research (ISR) ASCO 2026 Presentations Presentation TitleAuthorAbstract NumberPresentation DetailsUpdated analysis of overall survival with imetelstat in relapsed/refractory myelofibrosis versus real-world data, and assessment of real-world treatment patternsAndrew T. Kuykendall, M.D.#366Poster, Mon. June 1, 9:00 am -12:00 pm CDTUpdated protocol: IMproveMF, a Phase 1b trial of imetelstat + ruxolitinib in patients with intermediate-1/2 or high-risk myelofibrosisJohn O. Mascarenhas, M.D.#394bPoster, Mon. June 1, 9:00 am -12:00 pm CDT Please see the full presentations for important qualifications and limitations. About RYTELO (imetelstat)RYTELO is an oligonucleotide telomerase inhibitor approved in the U.S. for the treatment of adult patients with 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 GeronGeron 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 LR-MDS with transfusion-dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor 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 ThrombocytopeniaRYTELO 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. NeutropeniaRYTELO 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 ReactionsRYTELO 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 ToxicityBased 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 REACTIONSSerious 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.pdfUse 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) the potential of real-world analyses to provide additional context on how therapies such as RYTELO are being used in routine clinical practice and across more diverse patient populations; (ii) Geron’s efforts to expand its understanding of RYTELO in clinical practice; (iii) Geron’s expectations for multiple analyses emerging from investigator-sponsored research which will complement clinical trial data and help inform treatment decisions for people living with LR-MDS; (iv) the potential for telomerase inhibition to reduce proliferation and induce death of malignant cells; 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) Geron’s future opportunities and plans, including the uncertainty of the nature of, and the timing and reporting of data emerging from, investigator-sponsored and real-world evidence trials of RYTELO; (b) whether Geron overcomes potential delays and other adverse impacts that may be caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing, supply chain, pricing, coverage and reimbursement, market penetration, regulatory and healthcare challenges in order to obtain and maintain the financial resources for and meet expected timelines and planned milestones, including the financial resources necessary to support investigator-sponsored research of RYTELO; (c) Geron’s reliance on investigator-sponsored research, including risks related to Geron’s lack of control over such investigator-sponsored research of RYTELO and the risk that investigator-led clinical trials over which Geron has no control could show marginal efficacy and/or clinically relevant safety concerns that could delay, limit or preclude the further clinical development, marketing approval and/or commercialization of RYTELO in any indication; (d) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (e) whether any future safety or efficacy results of RYTELO treatment cause its benefit-risk profile to become unacceptable; (f) whether imetelstat actually demonstrates disease-modifying activity in patients, including transfusion independence in LR-MDS, and the ability to target the malignant stem and progenitor cells of the underlying disease; (g) whether Geron meets its post-marketing requirements and commitments for RYTELO; and (h) whether there are failures or delays in manufacturing or supplying sufficient quantities of RYTELO (imetelstat) or other clinical trial materials that negatively impact the conduct and timing of clinical trials. 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, 2026, 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. Investor and Media:Dawn SchottlandtSenior Vice President, Investor Relations and Corporate Affairsdschottlandt@geron.com