WRHI 060 (ADVANCE): A Randomised, Phase 3 Non-inferiority Study of DTG + TAF + FTC Compared With DTG + TDF + FTC and EFV + TDF + FTC in Patients Infected With HIV-1 Starting First-line Antiretroviral Therapy - Extension to 192 Weeks

This is a non-inferiority (10% non-inferiority margin), study to assess the efficacy and safety of dolutegravir, DTG (50 mg once daily [QD]) administered in combination with tenofovir alafenamide fumarate, TAF (25 mg QD) and emtricitabine, FTC (200 mg QD) compared to DTG (50 mg QD) administered in combination with tenofovir disoproxil fumarate, TDF (300 mg QD) and FTC (200 mg QD) and compared to efavirenz, EFV (600 mg QD) administered in combination with TDF (300 mg QD) and FTC (200 mg QD) through 96 weeks in patients with HIV-1 starting first-line ART.

开始日期2017-01-16

申办/合作机构

University of the Witwatersrand

NCT02556268

/ Completed临床1期

Potential Pharmacokinetic Interaction of Human Immunodeficiency Virus (HIV) Antiretroviral Agents as Fixed-dose Combinations and Riociguat in HIV Patients

To investigate the pharmacokinetic drug-drug interaction potential of fixed dose antiretroviral therapies, i.e. ATRIPLA, COMPLERA, STRIBILD, TRIUMEQ, or any approved antiretroviral protease inhibitor in combination with (preferably) TRIUMEQ, on the exposure to riociguat in HIV patients on a stable dose of one of these therapies.
• To Assess the safety and tolerability of riociguat treatment in combination with these fixed-dose antiretroviral therapies.

开始日期2016-02-23

申办/合作机构

Bayer AG

100 项与依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯相关的临床结果

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100 项与依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯相关的转化医学

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100 项与依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯相关的专利（医药）

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605

项与依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯相关的文献（医药）

2026-03-01·Biochemistry and Biophysics Reports

Study on the processing transformation law of CATR and ATR in Xanthii Fructus and the metabolomics mechanism of their transformation products in LO2 cells

Article

作者: Wang, Lingling ; Ao, Huihao ; Huang, Cheng ; Hong, Yan ; Han, Yanquan ; Wu, Deling

Background:

The thermal processing of Xanthii Fructus is known to attenuate its hepatotoxicity. Carboxyatractyloside (CATR) and atractyloside (ATR), the primary toxic constituents, exhibit differential toxicity, with CATR being more potent. While the conversion of CATR to the less toxic ATR during processing is believed to underlie this toxicity reduction, the precise conversion dynamics and associated molecular mechanisms remain to be fully elucidated.

Purpose:

This study aimed to elucidate the mechanisms responsible for the reduced hepatotoxicity of Xanthii Fructus following sand-frying. We employed an integrated approach combining ultra-high-performance liquid chromatography (UHPLC), metabolomics, and network pharmacology to investigate the differences in chemical composition and toxicological pathways between the crude and processed herb.

Methods:

The UHPLC method was used to establish fingerprint of Xanthii Fructus from different origins before and after processing, and the contents of CATR and ATR were determined. The thermal conversion and comparative toxicity of these compounds were subsequently evaluated. Cellular metabolomics was performed to identify differential metabolites and perturbed pathways, while network pharmacology and molecular docking were used to predict and validate primary protein targets and their binding affinities.

Results:

The attenuated hepatotoxicity was primarily attributed to the thermal conversion of CATR to ATR. Metabolomic analysis revealed that CATR significantly impacted alanine, aspartate, and glutamate metabolism and the TCA cycle, whereas ATR predominantly affected pyrimidine, arginine, and proline metabolism. Glutathione metabolism was a common pathway for both. Molecular docking simulations showed that CATR exhibited a stronger binding affinity than ATR towards key protein targets (DSS, DESG2, and ENTPD1), which is consistent with its greater toxicity.

2026-02-01·JOURNAL OF ETHNOPHARMACOLOGY

Acorus tatarinowii Schott attenuates Alzheimer's disease via neuronal ferroptosis inhibition: A synergistic network pharmacology and multi-omics profiling study

Article

作者: Ou, Xianhong ; Wang, Yiling ; Zhang, Pan ; Wang, Lu ; Wu, Anguo ; Lai, Xiaodan ; Zhang, Shipeng ; Xiong, Rui ; Liu, Hengxu

ETHNOPHARMACOLOGICAL RELEVANCE:

The dried rhizome of Acorus tatarinowii Schott (ATR) is the most widely used traditional Chinese medicine for the treatment of dementia due to its effect of opening orifices and eliminating phlegm (Kai-Qiao-Huo-Tan in Chinese), reviving the mind and enhancing intelligence (Xing-Shen-Yi-Zhi in Chinese), but its mechanism remains not fully understood.

AIM OF THE STUDY:

To reveal the mechanism of ATR in the treatment of Alzheimer's disease (AD), which is a major type of dementia.

MATERIALS AND METHODS:

The effects of ATR on cognitive function and neuronal loss in APP/PS1 mice were evaluated by the novel object recognition test, nesting test, hematoxylin-eosin staining, and Nissl staining. The underlying mechanisms were studied by serum metabolomics, transcriptomics, network pharmacology, RT-PCR, Western blot, immunofluorescence, and immunohistochemistry.

RESULTS:

ATR significantly improved cognitive function, neuronal loss, and altered lipid metabolism in APP/PS1 mice. In β-amyloid (Aβ)_1-42 and ferric citrate (FC)-induced HT22 cells, ATR significantly improved the cell viability, reduced the intracellular free iron, reactive oxygen species, and lipid peroxidation, and transcriptome analysis showed that the mechanism was related to ferroptosis and iron metabolism. Network pharmacology analysis indicated that ATR may regulate Nrf2 signaling. Both in vitro and in vivo results showed that ATR increased the mRNA and protein expression of Nrf2 and GPX4. ATR also reduced brain iron deposition, downregulated TFR1, and upregulated FPN1 expression in APP/PS1 mice.

CONCLUSIONS:

ATR ameliorated AD by improving iron metabolism and inhibiting neuronal ferroptosis through activation of the Nrf2/GPX4 axis, which provided modern medical evidence for the use of ATR to improve AD.

2026-01-01·TOXICOLOGY LETTERS

The role of FOXO1/PPARγ in atrazine-induced hepatic lipid metabolism disorders

Article

作者: Ying, Qiao ; Haoyan, Ma ; Tong, Lu ; Xiaotong, Wu ; Yingchao, Huo ; Haotang, Zhao ; Yuezhu, Zhang ; Zengchen, Wang

As one of the most prevalently employed herbicides worldwide, atrazine (ATR) is widespread in the environment and is able to enter and impair the human body. Hepatic lipid metabolism disorders can be triggered by exposure to ATR. However, the underlying mechanism remains unclear. We performed a differential gene expression analysis using the NAFLD-related datasets GSE89632 and GSE160016 downloaded from the GEO database, both with the human liver as the samples. Then the GO and KEGG pathway enrichment analyses were performed. It was discovered that the FOXO1/PPARγ pathway might play a crucial role in hepatic lipid metabolism disorders. To confirm the hypothesis, forty 8-week-old male Wistar rats were randomly average exposed to different concentrations of ATR (0, 0.5, 5 and 50 mg/kg/d) by intragastric administration for 90 days. Then the liver tissue were isolated for histopathological observation; the levels of lipids were assessed by colorimetry; the expression of mRNA and protein was identified by Real-Time PCR and western blot. The findings demonstrated that the ATR-treated groups had higher levels of TC and TG in the liver; TC level in the serum was increased but TG level decreased. Besides, the expression of FOXO1, PPARγ, FASN, FABP4 and CD36 was also elevated. A correlation was observed between the lipid metabolism levels and the expression of FOXO1/PPARγ pathway genes. These results suggested that ATR can induce hepatic lipids accumulation by upregulating the expression of FOXO1/PPARγ. This study can offer insightful information for preventing and controlling risks related to agricultural residues.

项与依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯相关的新闻（医药）

2026-01-28

·PDXbank

ATR/PKMYT1抑制剂联合干预诱导Rb1缺失乳腺癌合成致死

Impact factor:14.7（2025） Published online：2025-12-24 研究背景乳腺癌是全球女性首位高发恶性肿瘤，亚型多、预后差异大。靶向细胞周期调控因子（如CDK4/6抑制剂）已成为ER+/HER2-晚期乳腺癌的标准治疗策略，但获得性耐药不可避免，Rb1蛋白的缺失是常见耐药机制之一。 Rb1（视网膜母细胞瘤蛋白）是G1-S期的重要调控因子，同时参与DNA损伤修复和有丝分裂检查点的维持。Rb1缺失会导致细胞周期失控，并增强对下游检查点（如ATR和PKMYT1）的依赖，导致乳腺癌细胞对CDK4/6 抑制剂的获得性耐药。 ATR（共济失调毛细血管扩张和Rad3相关激酶）调控S-G2期检查点，维持复制叉稳定；PKMYT1（膜相关酪氨酸/苏氨酸激酶1）调控G2-M期检查点，抑制CDK1过早激活。ATR 抑制剂 RP-3500 与 PKMYT1 抑制剂 RP-6306 正在开展 I 期 MYTHIC 试验（NCT04855656），但目前尚无明确生物标志物可预测其对乳腺癌的疗效。本研究发现Rb1 缺失通过削弱同源重组 (HR) 与非同源末端连接 (NHEJ) 修复能力，使乳腺癌细胞对 ATR/PKMYT1 联合抑制产生“合成致死”，Rb1 缺失/低表达可作为响应该联合策略的潜在标志物。研究结果 1、ATR/PKMYT1联合抑制在部分乳腺癌细胞中诱导合成致死为评估ATR抑制剂（RP-3500）和PKMYT1抑制剂（RP-6306）在乳腺癌中的治疗潜力，研究者在多种乳腺癌细胞系（TNBC细胞系：MB231、BT549、HCC1806、MB453和MB436；ER阳性细胞系：T47D和MCF7；CDK4/6抑制剂耐药株：MCF7PR）和非致瘤细胞（MCF10A和RPE）中评估了单药及联合用药的疗效。单药RP-6306在BT549、HCC1806和MCF7PR细胞中表现出显著的细胞毒性，而MCF7、T47D、MCF10A和RPE对药物敏感性较低；RP-3500对T47D和MCF10A影响较小，但对其他乳腺癌细胞表现出广泛活性（图1A）。相比RP-3500和RP-6306先后给药，同时给药可显著抑制BT549细胞的克隆形成（图1B）。进一步实验发现当RP-6306和RP-3500的摩尔比为3:1时，产生最佳协同作用（图1C-D）。AnnexinV染色显示，联合给药后在MCF7PR、BT549和MB436细胞（完全应答组CR）中凋亡显著增加，而MCF7、MB231和MB453细胞（非完全应答组Non-CR）几乎无凋亡反应（图1E）。研究者进一步在BT549和MCF7PR细胞中敲低PKMYT1，敲低后显著增强了细胞对RP3500的敏感性及凋亡水平（图F-I）。综上，ATR/PKMYT1联合抑制在部分TNBC和帕博西利耐药ER阳性乳腺癌中诱导细胞毒性，而在其他乳腺癌或非致瘤细胞中则无此效应。 2、Rb1缺失是预测ATR/PKMYT1联合治疗反应的关键生物标志物研究者利用RPPA蛋白芯片（图2A）和CCLE基因组数据发现，CR组细胞系（MCF7PR、BT549、MB436）均呈Rb1基因缺失且磷酸化Rb1蛋白水平显著降低（图2B-C），Westernblot进一步验证其Rb1蛋白完全缺失（图2D）。相反，Non-CR细胞系保留Rb1表达。曾被报道的ATR或PKMYT1抑制敏感性标志物（包括CCNE1扩增、FBXW7缺失或PPP2R1A缺失）在CR与非CR细胞间并无差异表达（图2C-E）。复制压力评分（图2F-G）及CCNE1扩增（图2H）在CR与非CR间无差异，无法预测协同效应，因此Rb1缺失是ATR/PKMYT1联合抑制最稳定、最特异的反应标志物。 3、Rb1缺失破坏细胞周期检查点并促进ATR/PKMYT1联合抑制后的DNA损伤为探究CR组细胞响应联合给药的驱动机制，研究者对单药及联合给药处理的CR与非CR细胞进行流式细胞术分析细胞周期。结果发现联合给药后，MCF7细胞G₁期占比增多，MCF7PR和BT549细胞G₂-M及亚G₁期细胞占比增多（图3A）。Westernblot显示E2F调控的周期蛋白差异：MCF7中CyclinA/B1（细胞S期及M期周期蛋白）下调，符合G₁阻滞；MCF7PR和BT549仍维持CyclinA/B1表达，提示检查点调控受损、周期继续推进；FOXM1（Rb1绕过效应因子）在CR模型中显著上调，使Rb1缺失细胞下持续增殖（图3B）。BT549中观察到有丝分裂异常及染色体断裂增多（图3C），PKMYT1敲低加重断裂，过表达则减少断裂但增加四倍体，说明多倍化源于检查点失调而非合成致死必需。DNA纤维实验显示：ATR抑制使CR细胞复制叉延伸长度缩短50%（图3D），联用PKMYT1抑制剂进一步缩短复制叉间距离，并促使DNA合成中的细胞提前进入有丝分裂，导致叉崩溃和DNA损伤累积（图3E）。 4、Rb1缺失是ATR/PKMYT1联合治疗敏感性的直接决定因素为直接验证Rb1状态是否决定敏感性，研究者对Non-CR细胞（MCF7、MB231）敲低Rb1，CR细胞（BT549、MCF7PR）诱导Rb1表达，进行联合给药并检测凋亡反应。结果显示Rb1敲低显著增加Non-CR细胞联合用药后的细胞凋亡，且单药效果不显著（图A-B）；诱导Rb1表达则保护CR细胞免于联合用药诱导的细胞凋亡，且单药效果不显著（图C-D）。通过克隆形成实验发现，MB231敲低Rb1后再进行联合给药，可显著减少细胞克隆形成，而BT549诱导Rb1表达则提升细胞克隆能力（图E-F）。通过中性彗星实验（检测DNA双链断裂），发现联合给药使BT549尾矩显著增加（DNA双链断裂增加），诱导Rb1表达后可逆转（图C）；MCF7/MB231敲低Rb1后，再进行联合给药导致DNA双链断裂增加，证实Rb1缺失加剧DNA双链断裂积累。 5、ATR与PKMYT1双重抑制在Rb1低表达乳腺癌PDX模型中诱导肿瘤完全消退研究者使用一组帕博西利耐药（PR）和三阴性（TNBC）患者来源异种移植（PDX）模型验证ATR/PKMYT1联合抑制的体内疗效。当小鼠肿瘤达100–120mm³时随机分组：RP-6306 20mg/kg每日两次（BID）、RP-3500 5mg/kg每日一次或两药联合，按3天给药4天停药周期治疗（图5A）。 PR4、TNBC2组接受联合治疗后出现完全肿瘤消退并显著延长小鼠生存期（图5B），PR2、PR3治疗组与对照组肿瘤无显著差异（图5C）。PR4、TNBC2组Ki67占比大幅降低，DNA双链断裂标志物（γH2AX）与凋亡标志（TUNEL）均显著升高（图5D）。且对未治疗的PDX模型肿瘤组织进行IHC，发现对联合用药无应答组（Non-CR组：PR2、PR3）组高表达Rb1，完全应答组（CR组：PR4、TNBC2）PR4几乎不表达Rb1，TNBC2仅弱阳性（图5E）。 6、Rb1缺失导致DNA修复通路功能缺陷研究者分析了来自乳腺癌PDX肿瘤组织和细胞系模型的RNA测序数据（图6A），结果显示CR PDX模型的DNA损伤修复通路基线表达显著降低（图6B）。DNA修复通路活性在PDX和乳腺癌细胞系模型中的分层证实，CR模型在双链DNA修复中持续表现出缺陷，包括同源重组（HR）和非同源末端连接（NHEJ），这被确定为Rb1缺乏肿瘤的一个标志性特征（图6C和D）。此外，Rb1诱导增强了Rb1缺乏CR模型中的NHEJ和HR修复活性（图D和E）。Rb1表达恢复后保护CR细胞免受核破坏，并显著增加RADS1（HR修复通路）和53BP1焦点（NHEJ修复通路）在ATR/PRKMT1处理后的招募（图6F和G）。这些发现表明Rb1在DNA修复中起着关键作用，其恢复可以增强DNA修复功能，从而在应对复制应激和检查点抑制时维护基因组完整性。 7、ATR/PKMYT1联合治疗激活JNK/p38介导的凋亡通路通过RNA测序和蛋白质组学分析（RPPA），研究者发现CR（MCF7PR和BT549）和Non-CR（MCF7和MB231）细胞系在处理后表现出不同的反应（图7A）。CR模型显示出应激反应通路的富集，包括炎症信号传导、p53激活和紫外线损伤反应（图7B），而DNA修复通路在ATR/PRKMT1处理后CR与非CR模型中表现出相反的调控（图5A）。此外，仅在CR中，额外的DNA损伤标志物（pS139-H2Ax、pS140-H2Ax和pS4/58-RP32）升高（图5A）。研究还发现，ATM激活是ATR抑制的下游结果，并且ATM不是细胞死亡的主要驱动因素（图7E-D）。相反，Rb1缺乏的细胞依赖于JNK/p38应激信号，可能由核糖体停滞触发，以驱动线粒体促凋亡和细胞死亡。这些发现表明Rb1缺乏的细胞在ATR/PRKMT1抑制后未能修复DNA损伤，激活JNK/p38应激反应通路，触发线粒体凋亡信号传导，导致ATR/PRKMT1联合抑制在Rb1缺乏的乳腺癌模型中的合成致死性。 8、Rb1缺失在转移性乳腺癌患者中与DNA修复缺陷和治疗抵抗相关通过分析癌症基因组图谱（TCGA）中的18例IV期乳腺癌病例，研究者发现Rb1缺陷不局限于单一乳腺癌亚型，而是代表了更广泛的基因组脆弱性（图8A）。使用Reactome数据库进行基因富集分析（GSEA）发现Rb1-intact（正常表达）肿瘤中DNA修复通路的显著富集，而Rb1缺陷肿瘤表现出DNA修复通路活性降低（图8B）。此外，本研究还检测了36名转移性管腔型乳腺癌患者的RNA测序数据，发现Rb1低肿瘤患者比Rb1高肿瘤患者显著更早进展（图8C）。Rb1缺失与DNA修复通路受损相关，预测对帕博利珠单抗的早期耐药，并增加肿瘤对DNA损伤疗法的敏感性，包括ATR/PRKMT1抑制、化疗和放疗。结论 ATR抑制剂（RP-3500）和PKMYT1抑制剂（RP-6306）联用在Rb1缺失的乳腺癌细胞中诱发合成致死，表现为细胞复制压力骤增，被迫提前进入有丝分裂，导致DNA损伤大量累积。在体外实验中，Rb1缺失的乳腺癌细胞表现出显著的凋亡和克隆形成能力降低。在体内实验中，Rb1缺失的PDX模型在接受ATR/PKMYT1抑制剂联合治疗后出现肿瘤消退，小鼠生存期显著延长；而Rb1正常的PDX模型治疗组与对照组肿瘤无显著差异，仅生存率有所提高。这些结果表明Rb1低表达可作为响应ATR/PKMYT1抑制剂联合策略疗效的生物标志物，为CDK4/6抑制剂耐药乳腺癌患者提供了潜在的治疗策略。免责声明：本号内容仅供读者学习和交流。文章、图片等版权归原作者享有，如有侵权，请留言联系南昌乐悠生物科技有限公司成功构建多例乳腺癌PDX模型和细胞株移植瘤（CDX和Syngenic），欢迎各种形式合作。有兴趣的请致电：4008-160-580。原文链接： PDF原文【PMID 4144249.pdf】欢迎关注我们的PDXbank公众号！公司简介：南昌乐悠生物科技有限公司是一家专业从事肿瘤动物模型构建及抗癌新药临床前药效评价的国家高新技术企业，已经为包括小分子靶向药、大分子靶向药（包括ADC）、溶瘤病毒、细胞药物（TIL、γδT）等多种抗癌新药研发提供了有力的支持，其中部分药物已经进入临床试验申请(IND)阶段。 REFERENCE： Jiang XT, Chen MK, Lee J, Rao X, Wang Y, Luo L, Wang J, Hunt KK, Keyomarsi K. Rb1 deficiency induces synthetic lethality with ATR and PKMYT1 coinhibition in breast cancer cell lines and patient-derived xenografts. Sci Transl Med. 2025 Dec 24;17(830):eadx6797. doi: 10.1126/scitranslmed.adx6797. Epub 2025 Dec 24. PMID: 41442499. 往期回顾： IL-8抑制剂联合溶瘤腺病毒可显著抑制复发性胶质母细胞瘤进展 TROP2靶向ADC与氧化磷酸化抑制剂联合应用有效抑制食管鳞癌进展 Cell Death Dis：靶向上皮膜蛋白2(EMP2)的ADC药物在肺癌体内外药效评价中展现出显著的抗肿瘤活性 HER2/HDAC2调控FOXA1乙酰化介导乳腺癌内分泌耐药的机制研究蛋白质组学与PDX模型为进展性恶性肿瘤筛选精准治疗靶点文字 | Kimi 复核 | 米粒排版 | 米粒

临床1期临床结果

2026-01-22

·张张和他的爸爸

巨兽的蜕变：吉利德科学(Gilead Sciences)企业史与金融资本战略

摘要本报告基于VestLab基金公司历史专家的视角，对吉利德科学（Gilead Sciences, NASDAQ: GILD）进行全景式、长周期的深度剖析。作为全球生物制药历史上最独特的样本之一，吉利德的发展史不仅是一部抗病毒技术的演进史，更是一部资本配置、专利博弈与商业模式重塑的教科书。本研究涵盖了从公司1987年创立至今的完整历程，深入探讨了其如何从反义核酸的迷雾中突围，建立起HIV领域的绝对霸权；如何在HCV（丙肝）领域通过“豪赌”实现登顶却又因“治愈诅咒”陷入增长陷阱；以及近年来在Daniel O'Day领导下向肿瘤学（Oncology）转型的艰难阵痛。报告将特别聚焦于吉利德在中国市场的独特路径——从迟到者到利用政策红利成为破局者，再到面临带量采购（VBP）与医保谈判（NRDL）的双重夹击。同时，我们将通过详实的财务数据，解构其自由现金流（FCF）机器的运作逻辑、研发投入（R&D）效率以及在资本市场上的估值迷思。这是一份关于科学、资本与人性的深度观察。第一章：基因里的冒险——从Oligogen的迷梦到小分子的觉醒（1987-1996）1.1 起源：登革热、哈佛MBA与Oligogen的诞生吉利德科学的故事始于1987年6月，最初的公司名称“Oligogen”充满了那个时代对基因工程的无限遐想。创始人迈克尔·赖岳丹（Michael L. Riordan）并非传统的药企高管，而是一位拥有约翰霍普金斯大学医学博士学位和哈佛商学院MBA学位的复合型人才。赖岳丹的创业动机源于一次深刻的个人危机——他在菲律宾的一家诊所工作时不幸感染了登革热。这种病毒性疾病的折磨让他意识到，尽管抗生素已经征服了细菌，但人类在对抗病毒方面几乎手无寸铁。在那个生物技术的洪荒年代，赖岳丹将Oligogen的技术赌注押在了一种名为“反义治疗”（Antisense Therapy）的前沿领域。其核心理念是通过制造特定的DNA小片段（寡聚体或寡核苷酸），精准靶向并阻断致病蛋白的基因编码序列。这在理论上是一种“上帝视角”的治疗方式——直接从基因层面封锁病毒的复制指令，而非仅仅在蛋白质层面进行对抗。为了支撑这一宏大的愿景，赖岳丹展现了极强的资本运作能力。他不仅说服了风险投资家，还吸引了当时的制药巨头葛兰素威康（Glaxo Wellcome，现GSK的一部分）入局。1990年，吉利德与葛兰素签署了合作协议，葛兰素提供数百万美元的资金支持吉利德开发遗传密码阻断剂。这笔资金对于初创期的吉利德至关重要，它不仅维持了实验室的运转，更为公司带来了大药企的背书。1.2 技术的死胡同与战略大转折然而，科学的理想往往受制于物理化学的现实。在整个90年代初期，吉利德的科学家们在反义核酸领域遭遇了难以逾越的障碍。反义寡核苷酸分子量大、带负电荷，极难穿透细胞膜进入细胞内部；即使进入，它们在体内也极不稳定，容易被酶降解；更致命的是脱靶毒性问题始终无法解决。虽然吉利德在1992年成功上市（IPO），募集了8600万美元，但核心技术的停滞让公司面临生存危机。此时，吉利德管理层展现出了极其罕见的战略果断性。他们意识到，如果继续死磕反义技术，公司可能会耗尽现金而亡。于是，一场静悄悄但惊心动魄的“降维打击”开始了——从复杂的基因疗法转向小分子核苷酸类似物（Nucleotide Analogs）。核苷酸类似物的化学结构相对简单，但设计精妙。它们模拟病毒复制所需的天然核苷酸（如腺嘌呤、胞嘧啶等），一旦被病毒的DNA聚合酶误用，就会像在拉链中卡入一颗坏齿，导致病毒DNA链的合成强制终止。相比于反义核酸，小分子药物具有天然的优势：口服吸收好、生产成本低、性质稳定。 1998年6月，吉利德正式宣布终止与葛兰素威康关于反义技术的合作，并将相关知识产权出售给Isis Pharmaceuticals（即后来的Ionis），彻底剥离了这一起家业务。这一决策在当时看来是承认失败，但站在历史的长河回望，这是吉利德凤凰涅槃的起点。1.3 第一次商业化闭环：Vistide的苦涩胜利在转型过程中，吉利德迎来了第一个获批药物——Vistide（西多福韦，Cidofovir）。1996年6月，FDA批准Vistide用于治疗艾滋病患者的巨细胞病毒（CMV）视网膜炎。 Vistide的获批具有多重意义：科学验证：它证明了吉利德在核苷酸化学修饰方面的能力，特别是通过磷酸酯化修饰提高药物细胞内稳定性的技术路线是可行的。商业试炼：吉利德借此建立了初步的销售团队，虽然Vistide的销售额从未达到重磅炸弹级别（年销售额仅数千万美元），但它让吉利德完成了从研发到商业化的全流程演练。局限性启示： Vistide需要静脉注射，且具有严重的肾毒性，患者必须同时服用丙磺舒并大量补液以保护肾脏。这种极其不便的给药方式让吉利德深刻意识到：抗病毒药物的决胜点不仅在于疗效，更在于给药的便利性（Convenience）。这一教训直接孕育了后来统治HIV市场的“每日一片”哲学。第二章：抗病毒帝国的崛起——John Martin与HIV特许经营权的建立（1996-2010）2.1 约翰·马丁（John Martin）时代的开启 1996年，Vistide获批的同时，吉利德迎来了一位改变公司命运的关键人物——约翰·马丁（John C. Martin）。马丁是一位拥有有机化学博士学位的科学家，此前在百时美施贵宝（BMS）负责抗病毒药物开发。与当时许多光鲜亮丽的制药CEO不同，马丁作风低调，不爱在媒体聚光灯下露面，甚至着装朴素，常穿平价的商务休闲装。但他在战略上的眼光却是极具侵略性的。马丁上任后，迅速确立了吉利德的战略核心：专注于抗病毒领域，追求极致的给药便利性。他敏锐地洞察到，当时的艾滋病治疗虽然有了“鸡尾酒疗法”（HAART），但患者每天需要吞服几十粒药片，不同药物的服用时间、饮食禁忌各不相同，导致患者依从性极差，不仅生活质量低，还容易诱发耐药病毒。马丁提出了一个在当时看来近乎幻想的目标：将艾滋病治疗简化为每天一片药（One Pill, Once a Day）。2.2 替诺福韦（TDF）：帝国的基石为了实现这一目标，吉利德将研发重心全部倾注在替诺福韦（Tenofovir Disoproxil Fumarate, TDF）上。TDF是Vistide的化学近亲，但经过了更精妙的前药修饰，使其能够口服吸收。2001年，FDA批准TDF（商品名Viread）上市。 TDF的出现是革命性的。它具有极长的半衰期，支持每日一次给药；它的耐药屏障极高，病毒很难通过突变绕过它的封锁；它的副作用在当时看来是可以接受的（尽管后来骨密度和肾毒性问题成为争议焦点）。Viread迅速成为HIV治疗方案中的首选骨干药物（Backbone）。2.3 资本并购与组合拳：构建Truvada 拥有了TDF这一基石后，马丁开始通过并购来寻找TDF的最佳搭档。收购Triangle Pharmaceuticals (2003年)： 2003年，吉利德斥资约4.64亿美元收购了处于困境中的Triangle Pharmaceuticals。这次收购被认为是制药史上性价比最高的交易之一。通过Triangle，吉利德获得了恩曲他滨（Emtricitabine, FTC）。FTC是一种核苷逆转录酶抑制剂，结构与葛兰素威康的王牌药物3TC（拉米夫定）相似，但半衰期更长，药效更持久。吉利德迅速将TDF与FTC结合，于2004年推出了二合一复方制剂Truvada（舒发泰）。Truvada的问世确立了吉利德在HIV市场的霸主地位。在随后的十几年里，Truvada几乎成为了所有HIV一线治疗方案的标配骨架，“吉利德骨架”成为了行业标准。2.4 Atripla：化敌为友与单片时代的到来 2006年，吉利德的“每日一片”战略迎来了巅峰时刻。当时，HIV治疗的标准三联疗法通常由吉利德的Truvada（两药）加上百时美施贵宝（BMS）的Sustiva（依非韦伦，第三药）组成。患者需要分别购买两个公司的药。为了实现真正的单片化，吉利德与竞争对手BMS达成了一项史无前例的合作：成立合资企业，将三三种成分压制成一片药。2006年7月，FDA批准了Atripla。这是全球首个完整的HIV单片复方制剂（Single Tablet Regimen, STR）。 Atripla的成功是毁灭性的。它不仅占据了极高的市场份额，更重要的是，它构建了极高的转换壁垒。一旦患者习惯了每天只需在睡前服用一片Atripla，他们就极难被竞争对手（如葛兰素威康、默沙东）那些每日需服用多次或多片的方案所吸引。2.5 持续迭代与Stribild/Genvoya 吉利德并未止步于Atripla。随着整合酶抑制剂（Integrase Inhibitor）的兴起，吉利德开发了自己的整合酶抑制剂埃替格韦（Elvitegravir），并推出了四合一药物Stribild（2012年）和Genvoya（2015年）。这一系列操作不仅更新了产品线，更重要的是逐步剔除了其他公司的成分（如BMS的依非韦伦），实现了全产业链利润的独享。到2010年代初，吉利德的抗病毒业务已成为一台超级印钞机，毛利率高达80%以上，自由现金流如潮水般涌入。这为公司后续在丙肝领域的惊天豪赌积攒了足够的筹码。第三章：丙肝（HCV）的淘金狂潮与“治愈”的代价（2011-2017）3.1 Pharmasset收购案：110亿美元的疯狂赌注 2011年，虽然HIV业务如日中天，但吉利德面临着长期的增长焦虑。HIV虽然是慢性病，但市场渗透率已高，且竞争对手也在不断进步。吉利德急需第二增长曲线。目光锁定在了丙型肝炎（HCV）。当时的HCV治疗是痛苦的：患者需要注射干扰素长达48周，副作用极类似化疗（脱发、抑郁、流感样症状），且治愈率仅为50%-70%。 2011年11月，吉利德宣布以110亿美元现金收购一家名为Pharmasset的小型生物科技公司。当时Pharmasset没有一分钱的销售收入，仅有一款处于临床II/III期的药物PSI-7977（后来的Sovaldi）。收购溢价高达89%，这一消息震惊了华尔街，吉利德股价当日暴跌，分析师纷纷指责出价过高，甚至有评论称这是“鲁莽的赌博”。然而，约翰·马丁和他的CSO（首席科学官）Norbert Bischofberger看准了PSI-7977的独特价值。这是一种核苷酸聚合酶抑制剂，具有极高的耐药屏障，且有望覆盖所有HCV基因型。更关键的是，它有望实现“去干扰素化”的全口服治疗。3.2 Sovaldi与Harvoni：不仅是药物，更是金融现象 2013年12月，FDA批准Sovaldi（索磷布韦）；2014年10月，复方制剂Harvoni（雷迪帕韦/索磷布韦）获批。效果是颠覆性的：12周全口服疗程，副作用极低，治愈率超过95%。这不再是治疗，这是治愈。吉利德的财务报表随之发生了核爆级的变化： 2014年：抗病毒产品销售额从2013年的93亿美元暴涨至228亿美元，主要增量来自Sovaldi。 2015年：总营收达到326亿美元，净利润高达181亿美元，自由现金流突破205亿美元。在短短两年内，吉利德不仅收回了收购Pharmasset的110亿美元成本，还赚取了数百亿美元的纯利润。这被哈佛商学院等机构列为医药并购史上最成功的案例之一。3.3 “千元药片”与定价伦理的全球激辩伴随着商业奇迹的，是滔天的舆论巨浪。吉利德将Sovaldi在美国的定价设定为每片1000美元，一个疗程（84片）需84,000美元；Harvoni更是高达94,500美元。这一高价策略引发了美国国会、保险公司和患者团体的强烈反弹。 2015年，美国参议院财政委员会发布了一份长达数百页的调查报告，严厉指责吉利德采取了“掠夺性定价”。报告披露的内部邮件显示，吉利德高层明知较低的价格可以让更多患者获得治疗，但为了最大化长期收入（特别是为了给后续更强的Harvoni留出定价空间），坚持了高价策略。吉利德的辩护逻辑是“价值定价”（Value-based Pricing）：丙肝若不治愈，会导致肝硬化和肝癌，肝移植的费用高达数十万美元。相比之下，8.4万美元的治愈费用实际上为医疗系统节省了开支。这一逻辑在经济学上站得住脚，但在伦理和政治上却面临巨大挑战。3.4 “治愈诅咒”与收入悬崖丙肝业务的辉煌是短暂的。这源于其商业模式的内在悖论：通过治愈消灭客户。与HIV或糖尿病需要终身服药不同，HCV患者一旦治愈，就永久退出了市场。随着积压的数百万重症患者在2014-2016年被快速治愈，患者池迅速枯竭。同时，竞争对手艾伯维（AbbVie）和默沙东（Merck）推出了具有竞争力的产品（如Mavyret），价格战爆发。 2016年： HCV销售额开始下滑，从2015年的191亿美元降至148亿美元。 2017年及以后：跌势不止，HCV业务迅速从公司的增长引擎变成了拖累。吉利德的股价也随之陷入长达数年的低迷，PE值长期徘徊在个位数，陷入了典型的“价值陷阱”。第四章：战略迷茫与向肿瘤学的艰难跨越（2017-2019）4.1 现金过剩与管线焦虑 2016-2017年间，吉利德账上躺着超过300亿美元的现金，但投资者却对其未来充满疑虑。HCV业务崩塌，HIV业务面临TDF专利悬崖。吉利德急需并购来填补增长真空。4.2 Kite Pharma收购案：进军细胞治疗的桥头堡 2017年8月，吉利德宣布以119亿美元收购Kite Pharma，正式进军CAR-T（嵌合抗原受体T细胞）免疫治疗领域。这次收购标志着吉利德从“小分子化学”向“活体细胞生物学”的跨越。然而，这次跨越比预想的要艰难得多。CAR-T疗法（如Yescarta）是个体化定制药物，需要从患者体内提取T细胞，冷链运输至工厂进行基因改造，扩增后再运回医院回输。物流炼狱：这种“静脉到静脉”（Vein-to-vein）的制造流程极其复杂，容错率为零。吉利德不得不投入巨资在全球建设细胞工厂，解决供应链瓶颈。减值冲击： 2019年，吉利德对Kite的资产进行了8亿美元的减值，原因是放弃了Kite-585（抗BCMA细胞疗法）的开发。市场开始质疑吉利德是否为Kite支付了过高的溢价。尽管如此，Yescarta和Tecartus的销售额逐年攀升，2023年细胞治疗业务销售额已接近20亿美元，证明了其临床价值，但相比HCV时代的爆发力，细胞治疗更像是一场长跑。第五章：Daniel O'Day时代与“三支柱”战略的重塑（2019-至今）5.1 罗氏风格的注入 2019年3月，来自罗氏制药（Roche）的Daniel O'Day接替John Milligan出任CEO。O'Day的到来标志着吉利德管理风格的根本转变。与前任John Martin的极简主义和科学家气质不同，O'Day带来了大型跨国药企（Big Pharma）的运营体系和对肿瘤学的执着。 O'Day提出了新的战略框架：建立**病毒学（Virology）、肿瘤学（Oncology）、炎症（Inflammation）**三大支柱。5.2 Immunomedics收购与Trodelvy的豪赌为了快速充实肿瘤管线，2020年，吉利德再次出手，以210亿美元收购Immunomedics，获得了核心资产Trodelvy（Sacituzumab govitecan）。这是一款靶向TROP-2的抗体偶联药物（ADC），在难治性的三阴性乳腺癌（TNBC）中表现优异。这次收购溢价率高达108%，显示了O'Day的决心。然而，整合过程并非一帆风顺。减值再现： 2024年，吉利德计提了约17.5亿美元的IPR&D减值，主要归因于Trodelvy在非小细胞肺癌（NSCLC）等适应症上的临床进展不及预期。市场分歧：投资者对吉利德在肿瘤领域的资本配置效率表示担忧。相比于Pharmasset的精准一击，Immunomedics的收购显得昂贵且风险更高。5.3 HIV的防守反击：Biktarvy与Lenacapavir 在激进转型肿瘤的同时，吉利德必须守住HIV这一现金奶牛。 Biktarvy的统治力： 2018年获批的Biktarvy（必妥维）是吉利德现有最强的STR产品，集合了TAF的安全性与整合酶抑制剂的高效性。2024年，Biktarvy全球销售额达到134亿美元，同比增长13%，占据了美国HIV治疗市场的半壁江山。 Lenacapavir的未来：吉利德正在押注下一代长效药物Lenacapavir（Sunlenca）。这是一种衣壳抑制剂，可实现每6个月一次皮下注射。2024年公布的数据显示，其在HIV预防（PrEP）中实现了100%的保护率。华尔街分析师预测，这将开启HIV预防的新时代，峰值销售额有望突破40亿美元。第六章：吉利德在中国——迟到者、破局者与博弈者6.1 迟到的入场与“吉利德速度” 相比于阿斯利康、辉瑞等深耕中国数十年的跨国药企，吉利德进入中国市场的时间极晚。直到2016-2017年，随着中国药政改革加速创新药审批，Sovaldi才在中国获批。然而，吉利德展现了惊人的追赶速度。在短短两年内，公司将全球核心的HCV（索磷布韦、丙通沙、夏帆宁）和HIV（必妥维、捷扶康）全线产品引入中国。6.2 医保谈判（NRDL）的生死战在中国，吉利德面临着独特的市场环境：庞大的患者基数与有限的支付能力。 HCV价格跳水： 2019年的国家医保谈判是吉利德中国战略的分水岭。面对歌礼制药等本土企业的竞争，吉利德采取了激进的以价换量策略。丙通沙（Epclusa）等药物的谈判价格降幅超过85%，每疗程费用从数万元降至数千元人民币。战略结果：虽然单价暴跌，但吉利德成功通过医保覆盖了广阔的县域市场，迅速清退了本土竞争对手，确立了在HCV领域的统治地位。 HIV领域的策略：必妥维（Biktarvy）随后也进入医保。数据显示，中国医保对创新药的平均压价幅度在60%左右。吉利德通过这一策略，使得Biktarvy在中国市场的销量在2023-2024年实现了强劲增长，成为跨国药企在中国极少数仍能保持高速增长的单品之一。6.3 商业化现状与挑战 2024年财报显示，吉利德在中国的业务表现强劲，但这背后暗流涌动。带量采购（VBP）威胁：随着TDF等老药专利过期，VBP导致原研药市场份额被仿制药大幅侵蚀。新产品接力：吉利德必须依靠不断引入Lenacapavir、Trodelvy等新药来对抗VBP带来的收入侵蚀。2025年，Trodelvy在中国市场的商业化表现将是检验其中国团队执行力的试金石。第七章：财务解构与资本效率分析7.1 自由现金流（FCF）：核心资产的护城河年份自由现金流 (FCF, 十亿美元) 备注 2015 20.5 HCV巅峰期，历史最高值 2021 10.8 疫情期间Veklury (瑞德西韦) 贡献显著 2022 8.3 资本开支增加 2023 7.4 并购与研发投入加大 2024 10.3 强劲反弹 (+39%)，核心业务复苏吉利德的FCF生成能力在生物医药行业无出其右。即使在转型阵痛期，其FCF也从未低于70亿美元。这为其持续的分红（股息率约4%）和债务偿还提供了安全垫。7.2 研发投入（R&D）与效率 2024年，吉利德的研发投入占营收比例约为21%（约59亿美元），这一比例在行业中处于中上水平。然而，如果算上收购带来的IPR&D减值，其实际资本消耗远高于此。与安进（Amgen）相比，吉利德的研发效率在过去五年备受争议。安进通过更稳健的自研和补充性收购维持了较高的ROIC，而吉利德的大手笔收购拉低了短期回报率。但随着肿瘤管线的成熟，这一趋势有望在2025-2026年反转。7.3 估值分析：走出“价值陷阱”？长期以来，吉利德的PE（市盈率）徘徊在10-12倍，远低于行业平均的15-18倍。这反映了市场对其“后HCV时代”增长可持续性的深度怀疑。然而，2024年下半年以来，随着Lenacapavir数据的公布和肿瘤业务的企稳，吉利德股价表现强劲，PE估值开始修复。市场开始重新审视其作为“高分红+抗衰退+有期权（肿瘤/长效HIV）”的独特配置价值。第八章：企业文化与内部张力8.1 两种文化的碰撞从John Martin时代的“抗病毒精英特种部队”到Daniel O'Day时代的“泛科室大型制药公司”，吉利德经历剧烈的文化震荡。旧吉利德：极度聚焦、决策极快、以科学为导向、成本控制严格。新吉利德：矩阵式管理、流程复杂化、以商业和肿瘤学为重心。这种转变导致了显著的人才流失和内部摩擦。Glassdoor等平台上的员工反馈显示，关于“重返办公室”政策的争议以及研发重心的转移引发了老员工的不满。此外，将生物制剂生产团队从加州Oceanside搬迁至Foster City总部的决定也导致了部分裁员和动荡。8.2 领导力风格对比特征 John Martin (1996-2016) Daniel O'Day (2019-至今) 背景化学家，科学家出身商业高管，罗氏体系出身核心战略极简主义，单片复方，抗病毒多元化，肿瘤/炎症，大并购着装/风格朴素，低调，务实精英化，公关导向，全球视野资本配置股票回购优先，精准并购激进并购优先，兼顾分红第九章：结论与前瞻9.1 穿越周期的生存智慧吉利德科学是一只在生物制药丛林中不断进化的怪兽。它曾因反义核酸的失败濒临绝境，却因转向小分子而重生；它曾因HCV药物太完美而“杀死”了自己的市场，却又在绝望中通过并购强行切入肿瘤赛道。它的历史证明了一条铁律：在制药行业，没有永远的护城河，只有永远的创新（或收购创新）。9.2 2025年及以后的看点 Lenacapavir的公共卫生效应：如果每半年一次的PrEP方案能获得医保和公共卫生系统的广泛买单，吉利德将从一家治疗疾病的公司转变为一家消灭传染病的公司，其社会价值和商业价值将重估。肿瘤学的盈利拐点： Trodelvy和细胞治疗业务何时能覆盖其高昂的并购成本和研发支出，实现正向的ROIC贡献，是O'Day能否连任的关键。中国市场的演变：在VBP常态化下，吉利德如何利用其创新药维持在中国的增长，将是跨国药企在华生存的样本。对于VestLab基金而言，吉利德不再是当年那个年复合增长率50%的成长股，而是一个现金流充沛、下行风险有限、且手握几张高赔率彩票（长效HIV、肿瘤ADC）的稳健配置标的。 🎙️ 推荐关注小宇宙播客，Youtube，VestLab，追问而非迎合，寻求理解而非流量。在真相面前，谦卑与质疑，比流量更重要。 Powered by VestLab Editor

2026-01-12

·PRNewswire

CytoSorbents Reports Preliminary Unaudited Fourth Quarter and Full-Year 2025 Results and Business Update

Fourth quarter and Full-Year 2025 revenue are expected to be approximately $9.2 million and $37.0 million, respectively, with expected Q4 gross margins in the range of 73% to 75% DrugSorb®-ATR De Novo Pre-Submission Meeting scheduled with the FDA this month, with anticipated De Novo Application filing this quarter and regulatory decision in mid-2026 Results of the pivotal STAR-T study for DrugSorb®-ATR have recently been accepted for publication in a top cardiac surgery journal Management will host in-person investor meetings in San Francisco during J.P. Morgan Healthcare Conference week PRINCETON, N.J., Jan. 12, 2026 /PRNewswire/ -- CytoSorbents Corporation (NASDAQ: CTSO), a leader in the treatment of life-threatening conditions in the intensive care unit and cardiac surgery using blood purification, today announced preliminary unaudited fourth quarter and full-year 2025 financial results and business update. Preliminary, Unaudited Selected Fourth Quarter and Full-Year Financial Results Fourth quarter 2025 revenue is expected to be approximately $9.2 million compared to $9.2 million in the fourth quarter of 2024 Full-year 2025 revenue is expected to be approximately $37.0 million, representing approximately 4% growth versus $35.6 million for the full-year 2024 Fourth quarter gross margin is expected to be in the range of 73% to 75%, compared to 71% in the fourth quarter of 2024, and 70% in the third quarter of 2025 Full-year gross margin is expected to be approximately 72%, compared to 71% for full-year 2024 Recent Business Updates Cumulative CytoSorb treatments have now surpassed 300,000 worldwide. Results of the pivotal STAR-T study for DrugSorb®-ATR have recently been accepted for publication in a top cardiac surgery journal. The publication is currently in press and should be available online soon. The Company has scheduled a Pre-Submission Meeting this month with the U.S. Food and Drug Administration (FDA) to confirm regulatory requirements for a new De Novo Application for DrugSorb®-ATR, the Company's investigational medical device to reduce the severity of perioperative bleeding in patients on ticagrelor (Brilinta®, AstraZeneca) undergoing coronary artery bypass graft (CABG) surgery. Pending the outcome of the Pre-Submission Meeting, the Company expects to file a new De Novo Application by the end of the first quarter of 2026. As previously announced, on November 13, 2025, the Company amended its credit agreement which strengthened its balance sheet with an additional $2.5 million of cash and extended the interest-only-period through December 31, 2026. The amendment also provides for an additional $2.5 million of cash and an additional extension of the interest-only period to June 30, 2027 with DrugSorb®-ATR FDA marketing approval. Further, the Company implemented a previously announced strategic workforce and cost reduction program in the fourth quarter and expects to be approximately cash-flow breakeven (excluding restructuring payments) for the first quarter of 2026. "First, we are very pleased with the acceptance of the STAR-T study results for publication in a prestigious cardiothoracic surgery journal, reflecting the interest and clinical relevance of our technology within the cardiac surgical community. We expect the publication to be available online very soon," commented Dr. Phillip Chan, Chief Executive Officer of CytoSorbents. "Next, we look forward to our scheduled Pre-Submission Meeting with the FDA later this month to discuss the additional information planned for inclusion in our upcoming De Novo filing. Since the initial De Novo submission in September 2024, substantial additional new real-world data have become available. These data demonstrate that the use of our device in routine clinical practice for patients on ticagrelor undergoing urgent CABG surgery is associated with lower rates of severe bleeding compared with rates previously reported in the literature when the device is not used. We believe this new information is consistent with recent FDA guidance emphasizing the value of real-world evidence in supporting benefit-risk assessments for investigational devices and, when combined with our STAR-T results, further strengthen the overall evidence base for our upcoming submission. Pending alignment with the FDA and submission of the new, updated De Novo submission, we continue to anticipate a regulatory decision in mid-2026. We look forward to completing the regulatory process and bringing DrugSorb®-ATR to market as a potential solution to this critical unmet need in cardiac surgery." "Meanwhile, we continue to progress with our operational changes designed to drive sustained, profitable growth in the long run. We have strengthened our balance sheet through an amendment of our credit facility. We are in the midst of implementing numerous process improvements to return our German commercial team to growth. We expect that these initiatives along with our recently implemented global strategic Workforce and Cost Reduction program will accelerate our path to profitability, and we continue to expect to be approximately operating cash flow break-even in the first quarter of 2026." Dr. Chan concluded, "Finally, we are pleased to have surpassed the milestone of 300,000 CytoSorb treatments delivered cumulatively worldwide, where the therapy has been used to help critically ill and cardiac surgery patients in a wide multitude of clinical applications. We are thankful for the opportunity to work with a global community of clinicians and scientists committed to solving major unmet medical needs like sepsis and septic shock, acute liver failure, acute respiratory distress syndrome, perioperative bleeding caused by blood thinners, and many other life-threatening conditions afflicting millions of people each year." The results disclosed in this press release are preliminary and unaudited. The Company expects to report full, audited results for the fourth quarter and year ended December 31, 2025, on March 11, 2026. Management will host in-person investor meetings in San Francisco alongside the 44th Annual J.P. Morgan Healthcare Conference being held January 12-15, 2025, in San Francisco, CA. To schedule a meeting with Dr. Phillip Chan, Chief Executive Officer, and Peter J. Mariani, Chief Financial Officer, please send requests to [email protected]. About CytoSorbents Corporation ( NASDAQ: CTSO ) CytoSorbents Corporation is a leader in the treatment of life-threatening conditions in the intensive care unit and cardiac surgery through blood purification. CytoSorbents' proprietary blood purification technologies are based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Cartridges filled with these beads can be used with standard blood pumps already in the hospital (e.g. dialysis, continuous renal replacement therapy or CRRT, extracorporeal membrane oxygenation or ECMO, and heart-lung machines), where blood is repeatedly recirculated outside the body, through our cartridges where toxic substances are removed, and then back into the body. CytoSorbents' technologies are used in a number of broad applications. Specifically, two important applications are 1) the removal of blood thinners during and after cardiothoracic surgery to reduce the risk of severe bleeding, and 2) the removal of inflammatory agents and toxins in common critical illnesses that can lead to massive inflammation, organ failure and patient death. The breadth of these critical illnesses includes, for example, sepsis, burn injury, trauma, lung injury, liver failure, cytokine storm and cytokine release syndrome, and pancreatitis as well as the removal of liver toxins that accumulate in acute liver dysfunction or failure, and the removal of myoglobin in severe rhabdomyolysis that can otherwise lead to renal failure. In these diseases, the risk of death can be extremely high, and there are few, if any, effective treatments. CytoSorbents' lead product, CytoSorb®, is approved in the European Union and distributed in over 70 countries worldwide, with more than 300,000 devices used cumulatively to date. CytoSorb® was originally launched in the European Union under CE mark as the first cytokine adsorber. Additional CE mark extensions were granted for bilirubin and myoglobin removal in clinical conditions such as liver disease and trauma, respectively, and for ticagrelor and rivaroxaban removal in cardiothoracic surgery procedures. CytoSorb® has also received FDA Emergency Use Authorization in the United States for use in adult critically ill COVID-19 patients with impending or confirmed respiratory failure. CytoSorb® is not yet approved or cleared in the United States. In the U.S. and Canada, CytoSorbents is developing the DrugSorb®-ATR antithrombotic removal system, an investigational device based on an equivalent polymer technology to CytoSorb®, to reduce the severity of perioperative bleeding in high-risk surgery due to blood thinning drugs. It has received two FDA Breakthrough Device Designations: one for the removal of ticagrelor and another for the removal of the direct oral anticoagulants (DOAC) apixaban and rivaroxaban in a cardiopulmonary bypass circuit during urgent cardiothoracic surgery. The Company is actively pursuing regulatory approval of DrugSorb®-ATR with the U.S. FDA and will pursue regulatory approval with Health Canada with better visibility from the FDA. DrugSorb®-ATR is not yet granted or approved in either the U.S. or Canada. The Company has numerous marketed products and products under development based upon this unique blood purification technology protected by many issued U.S. and international patents and registered trademarks, and multiple patent applications pending, including ECOS-300CY®, CytoSorb-XL™, HemoDefend-RBC™, HemoDefend-BGA™, VetResQ®, K+ontrol™, DrugSorb®, ContrastSorb, and others. For more information, please visit the Company's website at and follow us on Facebook and X and LinkedIn. Forward-Looking Statements This press release includes forward-looking statements intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, statements about our plans, objectives, future targets and outlooks for our business, representations and contentions, and the outcome of our regulatory submissions, and are not historical facts and typically are identified by use of terms such as "may," "should," "could," "expect," "plan," "anticipate," "believe," "estimate," "predict," "potential," "continue" and similar words, although some forward-looking statements are expressed differently. You should be aware that the forward-looking statements in this press release represent management's current judgment and expectations, but our actual results, events and performance could differ materially from those in the forward-looking statements. Factors which could cause or contribute to such differences include, but are not limited to, our restructuring of our direct sales team and strategy in Germany, ability to successfully obtain U.S. FDA and Health Canada marketing authorization or approval, our ability to complete our strategic workforce and cost reduction plan to reduce costs, optimize operations, and achieve cash-flow break-even in the first quarter of 2026, our ability to appropriately finance the Company, and the risks discussed in our Annual Report on Form 10-K, filed with the SEC on March 31, 2025, as updated by the risks reported in our Quarterly Reports on Form 10-Q, and in the press releases and other communications to shareholders issued by us from time to time which attempt to advise interested parties of the risks and factors which may affect our business. We caution you not to place undue reliance upon any such forward-looking statements. We undertake no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, other than as required under the Federal securities laws. Please Click to Follow Us on Facebook and X U.S. Company Contact: Peter J. Mariani Chief Financial Officer [email protected] Investor Relations Contact: Aman Patel, CFA & Adanna G. Alexander, PhD ICR Healthcare [email protected] SOURCE Cytosorbents Corp 21% more press release views with Request a Demo

上市批准财报突破性疗法

100 项与依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	依非韦伦/恩曲他滨/富马酸替诺福韦二吡呋酯	J05AR06	-

研发状态

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10 条最早获批的记录,

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适应症	国家/地区	公司	日期
HIV感染	美国	Gilead Sciences LLC	2006-07-12

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
结核	临床1期	美国	Sanofi	2012-12-01

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临床结果

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分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01778413 (A-TRI-WEEK, CTgov)	临床4期	HIV感染	61	Atripla (ATRIPLA Three Days a Week (3W))	網顧網醖艱憲憲願夢遞 = 壓積選夢糧鑰齋觸鬱餘選願鑰顧膚糧構壓製鑰 (窪淵憲積鹽餘顧艱觸壓, 鏇淵鹽憲憲鹹鏇鏇淵觸 ~ 範遞鹹網憲淵襯積範餘) 更多	-	2025-07-18
				Atripla (ATRIPLA One Time a Day (OD))	網顧網醖艱憲憲願夢遞 = 窪壓網積衊鹽衊獵製製選願鑰顧膚糧構壓製鑰 (窪淵憲積鹽餘顧艱觸壓, 鹹遞鑰艱齋鏇願膚選繭 ~ 顧夢齋衊襯夢淵積廠艱) 更多
NCT03048422 (IMPAACT 2010 (VESTED), Pubmed \| J Acquir Immune Defic Syndr)	临床3期	bone mineral density \| creatinine clearance	-	Dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF)	鑰繭鏇壓鏇廠夢選衊簾(構廠蓋築鏇膚艱繭選蓋) = 艱積艱淵鬱積襯蓋壓醖製鹹憲繭願網餘願憲齋 (簾憲衊網積餘願淵範網 )	积极	2024-10-01
				Dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF)	鑰繭鏇壓鏇廠夢選衊簾(構廠蓋築鏇膚艱繭選蓋) = 蓋憲夢鹽壓選壓簾艱鬱製鹹憲繭願網餘願憲齋 (簾憲衊網積餘願淵範網 )
NCT03122262 (ADVANCE trial, IAS2020)	N/A	HIV感染一线	1,053	TAF/FTC+DTG	鏇繭蓋築壓衊鹽蓋積積(製鏇鏇積鏇簾積夢積鹹) = 積齋鏇獵夢積齋獵膚艱積觸壓築憲淵繭衊製鑰 (顧鑰鏇選鑰築糧獵淵鏇 ) 更多	积极	2020-01-01
				TDF/FTC+DTG	鏇繭蓋築壓衊鹽蓋積積(製鏇鏇積鏇簾積夢積鹹) = 鑰製齋鹽艱夢襯積積醖積觸壓築憲淵繭衊製鑰 (顧鑰鏇選鑰築糧獵淵鏇 ) 更多
IAS2020	N/A	HIV感染	100	EFV/FTC/TDF	繭願積糧鬱壓積夢鑰積(壓鹽壓構膚選糧淵憲顧) = 鬱蓋鏇網鏇齋衊憲衊窪夢獵繭鑰齋網範膚鑰鹽 (鏇淵蓋鬱選壓鏇艱醖艱 ) 更多	-	2020-01-01
NCT01529749 (CTgov)	临床4期	纤维化 \| HIV感染 \| 神经认知障碍	48	EFV/FTC/TDF (EFV/FTC/TDF)	鑰觸選觸齋築鑰淵醖鏇 = 窪膚獵觸淵遞選憲積壓鑰衊糧廠願鑰鹽齋願餘 (積衊積鏇膚遞醖獵製夢, 憲鹽齋衊襯築顧鏇獵膚 ~ 膚鬱願繭艱蓋網憲簾糧) 更多	-	2019-08-02
				EFV/FTC/TDF+Losartan (EFV/FTC/TDF + Losartan)	鑰觸選觸齋築鑰淵醖鏇 = 積膚鏇鏇願壓範壓獵廠鑰衊糧廠願鑰鹽齋願餘 (積衊積鏇膚遞醖獵製夢, 糧淵築構範膚夢選鹹憲 ~ 窪範糧鹹範鹹顧壓夢艱) 更多
NCT02246998 (CTgov)	临床4期	HIV感染	72	STB+iohexol (STB + Iohexol)	範範淵築憲鬱齋餘膚醖(繭齋築衊糧淵憲獵網膚) = 憲廠製餘鏇壓鹽襯網鬱襯齋簾鬱糧築憲窪糧選 (餘壓鏇簾範憲窪鹽觸構, 23.28) 更多	-	2018-01-03
				ATV+iohexol+TVD+RTV (TVD + ATV/r + Iohexol)	範範淵築憲鬱齋餘膚醖(繭齋築衊糧淵憲獵網膚) = 淵廠築鏇襯構製鹹夢鏇襯齋簾鬱糧築憲窪糧選 (餘壓鏇簾範憲窪鹽觸構, 27.16) 更多
NCT03251690 (IAS2018)	N/A	HIV感染	246	Switching to TDF/FTC/RPV	觸築鹹鹹艱構顧醖淵壓(齋簾廠鬱選齋製願醖艱) = 構鹽鹽製鬱衊鹽廠糧衊獵鬱糧鏇蓋遞襯鑰餘餘 (鬱鹽獵鑰鏇鹹鹽夢願鬱 ) 更多	-	2018-01-01
				Continuing TDF/FTC/EFV	觸築鹹鹹艱構顧醖淵壓(齋簾廠鬱選齋製願醖艱) = 顧衊鑰製繭壓糧選積觸獵鬱糧鏇蓋遞襯鑰餘餘 (鬱鹽獵鑰鏇鹹鹽夢願鬱 ) 更多
NCT01352117 (AMC 067 \| REACT-KS, CTgov)	临床3期	艾滋病相关性卡波西肉瘤	192	etoposide+efavirenz/emtricitabine/tenofovir disoproxil fumarate (Arm A: ART Alone or With Delayed ET)	積廠觸襯衊窪鏇齋衊壓: P-Value = 0.911	-	2017-07-31
				etoposide+efavirenz/emtricitabine/tenofovir disoproxil fumarate (Arm B: ART With Immediate ET)
NCT01380080 (REMEMBER, CTgov)	临床4期	结核 \| HIV感染	851	Atripla+Efavirenz+Truvada+Rifampin/isoniazid FDC+Rifampin/isoniazid/pyrazinamide/ethambutol FDC (Arm A: Empiric)	獵膚衊製壓觸網鹹餘夢 = 積範製艱糧壓鏇簾鬱構窪窪夢願鬱艱簾蓋艱網 (衊鹹製蓋獵夢製齋構壓, 廠構鬱繭積衊構鹹繭選 ~ 簾構餘膚餘糧遞膚簾築) 更多	-	2016-02-23
				Atripla+Efavirenz+Truvada+Isoniazid (Arm B: IPT)	獵膚衊製壓觸網鹹餘夢 = 獵鹽艱鹹遞簾廠艱築憲窪窪夢願鬱艱簾蓋艱網 (衊鹹製蓋獵夢製齋構壓, 窪築蓋鏇廠鹽築鹽遞衊 ~ 獵蓋蓋鏇鏇鹽憲網鏇願) 更多
SALIF (IAS 12016 \| IAS 22016)	N/A	一线	424	TDF/FTC/RPV	築獵構膚願襯淵憲鹹鏇(壓夢繭蓋餘鏇憲鬱廠簾) = 廠糧繭衊鬱製鏇膚簾廠膚遞網願製齋齋網蓋願 (餘蓋衊窪夢獵艱廠膚鏇 ) 更多	积极	2016-01-01
				TDF/FTC/EFV	築獵構膚願襯淵憲鹹鏇(壓夢繭蓋餘鏇憲鬱廠簾) = 夢選選蓋鹽襯餘鬱觸淵膚遞網願製齋齋網蓋願 (餘蓋衊窪夢獵艱廠膚鏇 ) 更多