Methotrexate Sodium

随着关税大战的逐步升级，短期内中国血制品行业可能受到关税影响，其中尤其是人血清白蛋白。人血清白蛋白具有提高血浆渗透压，减少组织水肿，改善器官等功能。在休克患者的急救中具有重要意义。然而，我国人血清白蛋白市场长期依赖美国进口（进口占比约60%，长期依赖于CSL、Grifols等血制品巨头），而关税增加将直接推高进口产品成本，削弱其价格优势，摧毁其市场垄断地位。这对于我国人血清白蛋白产业相关公司可以说是一场巨大的机遇，而一直以来，政策层面也鼓励国产替代以解决供应安全与“卡脖子”问题。近期，央视就报道了一家通过种植水稻来获得人血清白蛋白的生物制药公司武汉禾元生物。在这个时间点进行报道绝非偶然，本文将对该公司技术平台和管线进行简单介绍。核心技术平台直击痛点一直以来，人血清白蛋白等血制品依赖于人血浆捐献，生产成本来说相对较高，还存在受到病毒污染的问题（例如长达半个世纪的英国血污染丑闻），而供应量本身也受限于人的捐献意愿。美国的血浆制品出口就基于美国人民相当广泛的卖血现象。尽管缺乏美国官方口径的数据，但是这一现象得到普遍认可。例如早先小红书就分享过这样的一个案例：一位留学生惊讶地发现美国同学竟然通过卖血得来的钱请客吃饭。在这种情况下，开发非人源的重组产品就有望解决目前的伦理，安全，产能不足，价格偏高问题。禾元生物的核心技术平台是OryzHiExp，该技术平台选择了非常适合大规模生产的农作物水稻作为生物反应器，通过基因工程使得重组蛋白特异性地在水稻胚乳细胞中表达。表达量达15-20g/kg糙米，远超传统微生物发酵技术，且原料储存稳定（常温保存3-5年），适合大规模生产。图：OryzHiExp平台工艺流程 来源：公司官网从该公司发布的信息来看，目前植物源的人血清白蛋白具有优秀的批间一致性，长期稳定性也高于血浆来源白蛋白，储藏稳定性质量相较于血浆来源白蛋白更好。在研管线和专利简介另外，可表达的重组蛋白也不单单局限于人血清白蛋白，根据专利和管线可查证，目前禾元生物利用水稻表达植物源重组蛋白还包括：人乳铁蛋白，人糜蛋白酶，瑞替普酶，人抗胰蛋白酶，长效生长激素，人纤维连接蛋白，人碱性成纤维细胞生长因子。其中核心管线HY1001的进度最快，预计在今年年内上市。近年来禾元生物甚至申请了重组人血清白蛋白（HSA）-药物偶联物专利，这种为人血清白蛋白加装药物载体偶联的方式可以将该类药物应用于癌症。临床上最早诞生的HSA化学偶联物MTX-HSA，是由甲氨蝶呤(methotrexate，MTX)与HSA的赖氨酸残基共价偶联而得。研究数据表明，MTX-HSA相比MTX，由于HSA的引入使得药物的半衰期显著延长，且产生了明显的肿瘤靶向性。而血浆来源的HSA由于其Cys34可能结合有某些重金属离子、谷胱甘肽或者半胱氨酸，导致HSA的巯基游离度低，不易于偶联物的制备。该公司的另外一核心技术平台OryzPur则主要着重于水稻蛋白杂质的提取与纯化工艺。通常只需1至3 个层析步骤，纯化后纯度可达到98-99.9999%以上，优化了成本问题。目前，禾元生物的核心管线HY1001（植物源重组人血清白蛋白）凭借低成本（单位成本7-10元/g，仅为血浆来源产品的50%以下）和规模化生产潜力（目前团队已建成了年产100万支注射液的智能工厂，正在建设年产1200万支注射液的规模化生产基地。），有望快速填补进口产品留下的市场空缺。总结总的来说，关税政策为禾元生物提供了进口替代窗口期，但其能否把握机遇取决于商业化效率与专利风险管控。若HY1001成功上市并快速放量，公司有望在3-5年内成为血制品领域的国产龙头，重构行业竞争格局。长期来看，植物源重组蛋白技术的突破或推动我国从血制品进口国转变为技术输出国。参考来源：http://www.oryzogen.com/view/313.htmlhttps://patentscope2.wipo.int/search/zh/detail.jsf?docId=WO2022089340&_cid=JP1-M96DKN-61431-1本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处········

March 17, 2025 -- Lirum Therapeutics, Inc. (“Lirum”), an innovative clinical-stage biopharmaceutical company focused on the treatment of debilitating diseases, announced today that its first data on LX-101 in Thyroid Eye Disease (TED) have been selected for presentation at the 51st Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS), March 15-20 in Tucson, Arizona. These new results demonstrate the ability of LX-101 to effectively target the underlying processes that drive TED pathogenesis. Principal findings demonstrate that LX-101 can: 1) inhibit TED-derived orbital fibroblasts; 2) decrease production of key inflammatory cytokines; 3) reduce production of pro-fibrotic components of the extracellular matrix; and 4) modulate activity of TED-derived T-cells. TED is a serious autoimmune disorder characterized by progressive inflammation, driven by activated orbital fibroblasts and infiltrating T-cells, that can lead to orbital tissue expansion, eye bulging (proptosis), double vision (diplopia), pain, vision impairment, and possible sight-threatening complications. The results will be presented by Lirum’s academic collaborator, Collynn F. Woeller, Ph.D., from the Flaum Eye Institute at the University of Rochester. LX-101 is a clinical stage, novel, payload-bearing, targeted therapy directed to IGF-1R. LX-101 enables precise delivery of methotrexate, a drug widely used in autoimmune disease and with a history of use in TED, directly to key effector cells contributing to disease (i.e. IGF-1R+ activated T-cells and orbital fibroblasts). As such, LX-101, directed to a clinically and commercially validated target, may offer a novel and differentiated approach to treating TED. Given these promising results and a strong scientific rationale, combined with LX-101’s novel mechanism of action and prior positive clinical experience in oncology, Lirum is planning new clinical trials with LX-101 in TED and cancer. Presentation Details Abstract#:337Title:LX-101, a Novel Payload-bearing Insulin-like Growth Factor-1 Receptor Targeted Therapy, Inhibits Thyroid Eye Disease InflammationDate/Time:Monday, March 17th at 5 PM MSTSession Title:Analytical Studies, Orbital and Eyelid Disorders Lirum is an innovative clinical-stage biopharmaceutical company focused on the treatment of debilitating diseases through the acquisition, development and commercialization of novel drug candidates with compelling mechanisms of action, regulatory pathways and commercial opportunities. Lirum’s lead candidate, LX-101, is a novel clinical-stage targeted therapy directed to the insulin-like growth factor 1 receptor (IGF-1R) with a differentiated mechanism of action. Lirum is developing LX-101 in oncology and autoimmune indications, including thyroid eye disease (TED). The content above comes from the network. if any infringement, please contact us to modify.