A Phase 1, Open-Label, Single Center, Dose Escalation Study of the Safety and Pharmacokinetics of mAb AZD5396 and mAb AZD8076 Delivered as dMAbs in Healthy Adults

This is a Phase 1, open-label, single center, dose escalation study to evaluate the safety, tolerability and pharmacokinetic profile of mAb AZD5396 and mAb AZD8076 following delivery of optimized dMAb AZD5396 and dMAb AZD8076 with Hylenex® Recombinant, administered by intramuscular injection (IM) followed immediately by electroporation (EP) using the CELLECTRA™ 2000 with Side Port needle device, in a 2-dose regimen (Days 0 and 3) or a 4-dose regimen (Days 0, 3, 28 and 31) in healthy adults.
The hypothesis is that the administration of dMAb AZD5396 and dMAb AZD8076 will be safe and associated with expression of mAb AZD5396 and mAb AZD8076 in serum.

开始日期2022-05-19

申办/合作机构

University of Pennsylvania

[+3]

NCT05629923

/ CompletedN/AIIT

EVALUATION OF COVID-19 VACCINATION EFFICACY AND CONTIXAGEVIMAB-CILGAVIMAB PROPHYLAXIS IN LIVER AND KIDNEY TRANSPLANT PATIENTS: PRELIMINARY STUDY

The goal of this observational study is to evaluate the immune response after COVID-19 vaccination in Liver(LT) and Kidney(KT) transplant recipient. The main question it aims to answer are:
* the evaluation of the antibody response after complete vaccination
* the efficacy of prophylaxis with long-acting-antibody prophylaxis (LAAB)
All LT and KT patients during follow-up have been enrolled. anti-COVID-19 title was obtained by Electrochemiluminescence Immunoassay (ECLIA) Test(Elyx, Roche). In the case of antibody level <100 IU/ml, patients were invited to prophylaxis with tixagevimab-cilgavimab(AZD7442, AstraZeneca). At three months, a follow-up was performed to assess any COVID-19 infection. At Six months another anti-COVID-19 title is obtained by ECLIA Test(Elyx, Roche) in LT and KT who undergo to LAAB.

开始日期2022-02-01

申办/合作机构

Università degli Studi di Roma Tor Vergata

100 项与替沙格韦单抗相关的临床结果

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100 项与替沙格韦单抗相关的转化医学

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100 项与替沙格韦单抗相关的专利（医药）

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项与替沙格韦单抗相关的文献（医药）

2025-07-01·LANCET INFECTIOUS DISEASES

Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial

Article

BACKGROUND:

Sipavibart is an anti-spike monoclonal antibody that neutralises SARS-CoV-2 with exceptions, including Phe456Leu-containing variants (eg, KP.2* and KP.3*). This trial assessed sipavibart efficacy and safety for prevention of symptomatic COVID-19 in participants who are immunocompromised.

METHODS:

In this ongoing, double-blind, international, phase 3 trial, we enrolled participants who were immunocompromised and aged 12 years or older at 197 hospitals, university health centres, and clinical trial units in 18 countries. Participants were randomly allocated 1:1 to a sipavibart group (intramuscular sipavibart 300 mg on days 1 and 181) or a comparator group (tixagevimab 300 mg-cilgavimab 300 mg on day 1 and placebo on day 181 or placebo on days 1 and 181), stratified by previous COVID-19 vaccination and infection status and use of tixagevimab-cilgavimab. The primary efficacy outcomes were symptomatic COVID-19 caused by any variant or symptomatic COVID-19 caused by non-Phe456Leu-containing variants within 181 days of dosing, assessed in the SARS-CoV-2-negative set, comprising all participants without a positive RT-PCR test for SARS-CoV-2 at baseline and who received at least one trial intervention dose. Safety outcomes for adverse events were assessed 90 days following the first dose and for serious adverse events throughout the study in the safety analysis set (ie, all participants who received at least one injection of sipavibart or comparator). This study is registered with ClinicalTrials.gov, NCT05648110.

FINDINGS:

Participants were screened from March 31 to Oct 27, 2023; 3349 participants (56·8% female) were randomly assigned: 1674 to the sipavibart group (five no first dose; 1669 sipavibart) and 1675 to the comparator group (nine no first dose; 1105 tixagevimab-cilgavimab and 561 placebo). Within 181 days of dosing, 122 (7·4%) of 1649 participants in the sipavibart group and 178 (10·9%) of 1631 participants in the comparator group had symptomatic COVID-19 due to any variant (relative risk reduction [RRR] 34·9% [97·5% CI 15·0 to 50·1]; p=0·0006), 54 (3·3%) participants in the sipavibart group and 90 (5·5%) participants in the comparator group had symptomatic COVID-19 due to non-Phe456Leu-containing variants (RRR 42·9% [95% CI 19·9 to 59·3]; p=0·0012), and 47 (2·9%) participants in the sipavibart group and 64 (3·9%) participants in the comparator group had symptomatic COVID-19 due to Phe456Leu-containing variants (30·4% [-1·8 to 52·5]). Adverse events occurred in 833 (49·9%) of 1671 participants in the sipavibart group and 857 (51·5%) of 1663 participants in the comparator group within 3 months of the first dose. One COVID-19-related death occurred in the comparator group. Serious adverse events considered related to trial intervention occurred in two (0·1%) of 1671 participants in the sipavibart group and seven (0·4%) of 1663 participants in the comparator group (none fatal). No serious cardiovascular or thrombotic events were considered to be related to sipavibart.

INTERPRETATION:

The primary analysis showed efficacy and safety of sipavibart in preventing symptomatic COVID-19 in participants who are immunocompromised when susceptible (ie, non-Phe456Leu-containing) variants dominated, although no efficacy was shown against resistant (ie, Phe456Leu-containing) variants that dominate as of November, 2024.

FUNDING:

AstraZeneca.

2025-06-01·CLINICAL MICROBIOLOGY AND INFECTION

Long-term outcomes of passive immunotherapy for COVID-19: a pooled analysis of a large multinational platform randomized clinical trial

Article

作者: Engen, Nicole ; Mena Lora, Alfredo J ; Self, Wesley H ; Williamson, John C ; Price, D Ashley ; Mathews, Gail ; Lundgren, Jens ; Murray, Thomas A ; Kitonsa, Jonathan ; Knox, Daniel B ; Mylonakis, Eleftherios ; Kim, Kami ; Reilly, Cavan ; Young, Barnaby Edward ; Siegel, Lianne K ; Sandkovsky, Uriel ; Jain, Mamta K ; Paredes, Roger ; Ramachandruni, Srikanth ; Holland, Thomas L ; Eriobu, Nnakelu ; Ginde, Adit ; Grandits, Gregory A ; Jensen, Tomas O ; Barkauskas, Christina ; Mourad, Ahmad ; Malin, Jakob J ; Vock, David ; Rapti, Vasiliki ; Higgs, Elizabeth

OBJECTIVES:

Passive immunotherapy, including monoclonal antibodies and neutralizing proteins, was used for the treatment of patients with COVID-19 during the pandemic. Accelerating COVID-19 Therapeutic Interventions and Vaccines-Therapeutics for Inpatients with COVID-19 (ACTIV-3/TICO) was a multinational, randomized placebo-controlled platform trial that evaluated the effectiveness of multiple passive immunotherapy agents in patients hospitalized with COVID-19. Given the long half-life of some agents studied, participants were followed for an extended period to assess the long-term efficacy and sustained safety of these agents.

METHODS:

We conducted a pooled analysis of individual participant data from four trials of ACTIV-3/TICO: sotrovimab, amubarvimab-romlusevimab, tixagevimab-cilgavimab, and ensovibep. Cox proportional hazards models were conducted to compare time to mortality and time to mortality or rehospitalization between participants receiving active agents vs. placebo through 18 months.

RESULTS:

A total of 2311 participants were enrolled between 16 December 2020 and 15 November 2021. Overall, 56.9% (1315/2311) received an active agent and 77.2% (1784/2311) of participants were unvaccinated for SARS-CoV-2. Median duration between symptom onset and enrolment was 8 days (interquartile range, 6-10), and most participants received remdesivir (92.1% [2129/2311]) and corticosteroids (70.4% [1627/2311]) before enrolment. There was no difference in mortality across all active (11.9% [157/1315]) vs. placebo (14.0% [139/996]) arms (hazard ratio, 0.87; 95% CI, 0.70-1.08). Furthermore, there was no difference in combined mortality or rehospitalization across all active (31.7% [417/1315]) vs. placebo (32.1% [320/996]) arms (hazard ratio, 0.96; 95% CI, 0.84-1.10).

DISCUSSION:

In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization.

TRIAL REGISTRATION:

NCT04501978.

2025-05-01·JOURNAL OF MEDICAL VIROLOGY

Comparative Analysis of Early COVID‐19 Treatment Efficacy in a Multicentric Regional Cohort in Italy: Emulation of a Series of Target Trials

Article

作者: Garattini, Silvia ; D'Abramo, Alessandra ; Mazzotta, Valentina ; Siciliano, Valentina ; Gavaruzzi, Francesca ; Nicastri, Emanuele ; Mastroianni, Claudio M. ; Girardi, Enrico ; Rosati, Silvia ; Lichtner, Miriam ; Falletta, Antonio ; Antinori, Andrea ; Andreoni, Massimo ; Gasperin, Andrea ; Lanini, Simone ; Matteini, Elena ; Milozzi, Eugenia ; Marocco, Raffaella ; Vergori, Alessandra ; Cerva, Carlotta ; Gramigna, Giulia ; Cimaglia, Claudia ; Del Borgo, Cosmo ; Rueca, Martina ; Lepri, Alessandro Cozzi ; Maggi, Fabrizio ; Sarmati, Loredana ; Mastrorosa, Ilaria ; Giannico, Giuseppina ; Torti, Carlo ; Carraro, Anna ; Matusali, Giulia ; Coppola, Luigi ; Fantoni, Massimo ; Meschi, Silvia ; Oliva, Alessandra ; Piselli, Pierluca

ABSTRACT:

Studies comparing all available strategies for the early treatment of mild‐to‐moderate COVID‐19 during the Omicron era are lacking. We included people with mild‐to‐moderate COVID‐19 and at high risk of progressing to severe disease attending five outpatient clinics in Italy over 2022–2023. The primary outcome was the proportion of participants who experienced Day‐30 hospitalization due to COVID‐19 or death. Participants received either nirmatrelvir/ritonavir (NMV/r), molnupiravir (MLP), remdesivir (RDV), sotrovimab (SOT), or tixagevimab/cilgavimab (TIX/CIL). We included 10 038 individuals: females 5052 (50%), median age 71 years (IQR 59–81). In total, 1919 (19%) received SOT, 3732 (37.2%) MLP, 1444 (14%) RDV, 2510 (25%) NMV/r, and 433 (4%) TIX/CIL. Only 1689 (17%) had incomplete vaccination, and 2435 (24.3%) were not immunocompetent. The rate of hospitalization/death was 2.40% (95% CI 2.10–2.71). Unadjusted rates were 0.88% (95% CI 0.55–1.32) for NMV/r, 1.69% (95% CI 1.30–2.15) for MLP, 3.0% (95% CI 1.61–5.08) for TIX/CIL, 3.54% (95% CI 2.76–4.47) for SOT and 5.12% (95% CI 4.05–6.39) for RDV. Weighted analysis showed that NMV/r and MLP were superior to all other interventions. In our population of individuals at high risk of progression to severe disease, there was clinical benefit in using NMV/r or MLP instead of mAbs‐based therapies or RDV.

项与替沙格韦单抗相关的新闻（医药）

2025-05-27

·三优生物医药

三优生物智能超万亿分子发现平台六类分子形式之单域抗体产生系统解决方案

作者：巫嘉美闫鑫甜美工：何国红罗真真排版：马超01 背景在三优生物超万亿分子发现平台中，单域抗体产生平台占据重要地位。单域抗体最初发现于骆驼科动物（如羊驼、单峰驼）及软骨鱼类（如鲨鱼、鳐鱼），其显著特征是天然缺失轻链，仅由重链构成。作为新一代抗体药物的代表，单域抗体分子量小、稳定性高、抗原亲和力强，已在全球范围内广泛应用于免疫治疗、肿瘤治疗、抗病毒治疗等领域。为加速优质单域抗体的开发进程，三优生物隆重推出磁阵列羊驼免疫抗体发现平台、万亿级人源化单域抗体发现平台、千亿级高等电点单域抗体发现平台等三大平台，为单域抗体的创新研发提供全方位支持。02 文库组成三优智能超万亿单域库主要由三大文库组成。2016年三优生物推出磁阵列羊驼免疫抗体库，可选择多种品系驼科动物进行免疫，并辅以多样化的免疫方案和佐剂，先导抗体数量通常可达数十至上百。2022年三优生物推出万亿级人源化单域抗体库，采用人源化程度高达98%的骨架，融合国际先进的引物合成技术进行文库构建，并同时设计分别含有一对和两对半胱氨酸的子库，匹配不同场景的应用，先导分子通常可达数百。2025年三优生物推出千亿级高等电点单域抗体库，引入AI驱动的引物设计，精准控制等电点在8.0-9.0之间，并剔除了翻译后修饰位点，提高抗体在体内的稳定性，减少非特异性结合。三优智能超万亿单域抗体发现平台覆盖不同类型的单域抗体库，为单域抗体开发提供系统的全流程解决方案（如表1所示）。▼ 表1. 智能超万亿单域库三大文库03 磁阵列羊驼免疫抗体发现平台01平台概览三优磁阵列(MIT)羊驼免疫抗体发现平台整合了“阵列化羊驼免疫、阵列化噬菌体抗体库构建、磁珠高通量筛选、CHO真核细胞重组表达”四种技术，并匹配了全面的理化及生化分析进行筛选，仅需6-8周（从羊驼免疫结束开始）即可获得特异性好、亲和力高、序列明确、并经真核表达验证的羊驼单克隆抗体。02平台经验三优生物通过十年的积累，已完成559个羊驼免疫库的构建（如图1所示），累计库容达到2.93千亿，并完成了223个项目的筛选，靶点类型覆盖单次跨膜、多次跨膜、GPCR类、因子类、病毒类和胞内靶点。如表2所示，目前通过三优磁阵列羊驼免疫抗体发现平台获得的优选分子，已经有5例获得IND批件，其中4例正在进行临床Ⅰ期实验。▲ 图1. 羊驼免疫库建库数量统计▼ 表2. 三优生物IND获批单域抗体清单03服务特性▶ 特性一：磁阵列免疫、建库及筛选体系三优生物磁阵列羊驼免疫抗体发现平台集阵列化抗原、阵列化佐剂、阵列化建库、阵列化筛选、阵列化表达于一体（如图2所示）。阵列化抗原即针对不同类型的靶点，选择适合的免疫原及多样化的免疫策略，如蛋白、细胞、VLP、膜蛋白、mRNA或灭活疫苗等；阵列化佐剂包括弗氏佐剂、铝佐剂、寡核苷酸佐剂、Bol佐剂或FastAb佐剂等；阵列化建库通过设计阵列化的引物进行自动化文库构建，进一步保证文库的多样性；阵列化筛选通过多样化海选方案，如：固相海选、液相海选、细胞海选、固相液相交叉、蛋白细胞交叉、竞争海选等，基于一站式高通量自动化筛选系统，保证获得数十多样性高亲和力高的先导分子；阵列化表达通过96孔板进行高通量表达，并对真核表达蛋白进行系统的成药性分析。▲ 图2. 多样化免疫与海选方案 ▶ 特性二：先导抗体数量通常可达数十个通过三优MIT羊驼单克隆抗体定制服务筛选获得的单域抗体先导分子数量较多。如图3所示，通过10个靶点对MIT羊驼库进行验证，共获得475个具有独特序列的抗体克隆，克隆数中值为38个。▲ 图3. 项目的抗体数量统计▶ 特性三：羊驼免疫后血清学效价高图4展示的是免疫后羊驼血清学效价的数据。如图所示，该项目1只羊驼（A）免疫后的IgG血清学效价约为364万，血清效价高。▲ 图4. 羊驼血清效价检测▶ 特性四：羊驼免疫库建库质控标准高表3展示的是三优羊驼免疫抗体库构建质控理论指标和某单域库实际质控参数。如表3所示，8项质控参数均优秀达标，具有免疫效价高，库容大，空载体占比、终止子占比极低，抗体正确表达率和独特序列克隆率近100%的特点。▼ 表3. 项目的理论指标与实际指数▶ 特性五：先导抗体亲和力高通过三优MIT羊驼单克隆抗体定制服务筛选获得的单域抗体候选分子亲和力高，可达nM-pM水平。对所得单域抗体克隆构建全长IgG后的亲和力测定情况如下所示。图5展示了采用ELISA分析抗体与抗原蛋白结合活性的一个项目案例，由图可知，该项目获得多个亲和力与对照抗体相当或显著优于对照抗体的分子。图6展示了采用FACS分析抗体与细胞表面蛋白结合活性的项目案例，由图可知，全部先导抗体分子均展现了良好的细胞水平的结合活性。▲ 图5. ELISA分析抗体与抗原蛋白活性检测▲ 图6. FACS分析抗体与细胞表面蛋白活性检测代表案例：抗HER2/PD-L1/VEGF三抗开发01靶点背景HER2属于RTK类中HER家族一员，通过自身二聚化或和其它HER家族成员二聚化激活胞内信号通路，促进细胞的增殖，导致肿瘤细胞恶性程度增加。VEGF为血管生成关键调控因子，当VEGF表达上调会引起血管异常增生，因此，VEGF是存在病理性血管生成相关疾病的重要药物靶点。PD-L1是免疫检查点PD-1的配体，两者的结合能够促进T细胞的凋亡，抑制T细胞的抗肿瘤活性，多种肿瘤通过表达PD-L1来逃避免疫系统的监视。临床数据显示，靶向HER2、PD-1/PD-L1或VEGF的单抗联用具有协同抗肿瘤效应，能够延长肿瘤患者无进展生存期和总体生存且相比单抗未出现新的不良反应信号。目前已有靶向HER2/PD-1，HER2/PD-L1、HER2/VEGF，PD-1/VEGF的双抗处于临床或临床前研究阶段，其中康方生物开发的靶向PD-1/VEGF双抗AK112已表现出积极的临床药效，AK112联合化疗在NSCLC中的ORR为53.8%，DCR为100%。基于已有临床数据的协同效应，三优生物开发了靶向HER2、PD-L1和VEGF的三特异性抗体，该三抗集ADCC、肿瘤细胞增殖抑制、血管生成抑制和免疫检查点阻断多种抗肿瘤机制于一体，具有良好的体内外抗肿瘤活性（如图7所示）。▲ 图7. 针对HER2/PD-L1/VEGF的三特异性抗体的机制02三特异性抗体构型利用三优超万亿抗体平台筛选的PD-L1、VEGF单域抗体与已披露专利的HER2抗体构建成对称型三特异性抗体（如图8所示）。项目处于PCC阶段，为全球第一个针对P、H和V靶点三靶点的三特异性抗体，主要适应症为H+实体瘤。▲ 图8.三特异性抗体的分子构型03P/H/V 三特异性抗体关键结果A 细胞水平的结合、阻断分析：采用FACS分析候选抗体与细胞的亲和力及阻断测定结果。图9展示了候选抗体的亲和力水平与HER2和PD-L1对照抗体相当。利用荧光报告系统检测候选抗体在细胞水平的阻断，结果如图10所示，候选抗体的阻断水平与VEGF和PD-L1的对照抗体相当。▲ 图9.通过FACS进行结合亲和力测定▲ 图10. 通过FACS进行阻断活性测定B 体外药效验证：候选抗体可以通过ADCC对靶细胞进行杀伤，如图11所示，候选三抗TsAb1对SK-BR-3细胞的ADCC杀伤效果与对照抗体相当。如图12所示，候选抗体可有效抑制HUVEC细胞的增殖，效果与对照抗体相当。▲ 图11. SKBR-3细胞上的ADCC检测▲ 图12. 人内皮细胞增殖抑制C 体内药效验证：在PBMC免疫重建的某荷瘤NCG小鼠模型中，靶向P/H/V的三特异性抗体TsAb1具有比已上市靶向H单抗X1、靶向P单抗X2和靶向V单抗X3单药以及X1与X2联用和X2与X3联用更为显著的体内抗肿瘤活性。如图13所示，给药结束时，高低剂量的三抗治疗所产生的肿瘤抑制率分别为81.56%和67.34%，高于联合用药组和单抗治疗组。▲ 图13. 肿瘤生长抑制04 万亿级人源化单域抗体发现平台01平台概览单域抗体的人源化可以大幅降低驼源抗体的免疫原性，加速抗体药物的生产上市。为了克服传统单域抗体制备技术的制备周期长、筛选工作量大、候选抗体数量少的缺陷，三优隆重推出人源化程度高达98%的万亿级人源化单域抗体库。该文库共包含16个子库，总库容达到了4.07万亿，平均每个子库的库容为2.54千亿。万亿级人源化单域抗体库分为2C型单域抗体库和4C型单域抗体库，2C型单域抗体库CDR3长度覆盖12-19个氨基酸，4C型单域抗体库CDR3长度覆盖14-21个氨基酸（如表4所示）。▼ 表4. 万亿级人源化单域抗体库相关统计02平台经验三优万亿级人源化单域抗体发现平台，采用国际先进的引物合成技术以及具有较好成药性的人源化骨架构建而成，拥有独立知识产权，并匹配了全面的理化及生化分析进行筛选。仅需5-6周即可获得特异性好、亲和力高、序列明确并经真核表达验证的人源化单克隆抗体，人源化程度高达98%。如图14所示，针对不同难度的靶点，单库平均可获得227个序列独特、特异性好、亲和力经验证的先导抗体克隆。▲ 图14. 针对不同难度靶点获得的先导抗体克隆统计03服务特性▶ 特性一：人源化程度高三优构建的万亿人源化单域抗体库具有较高的人源化程度。通过130多个单域抗体分子的人源化项目经验积累，对单域抗体的骨架区（FR区）进行人源化改造，可以获得人源化程度高达98%的单域抗体，从而提高抗体的成药性（如图15所示）。▲ 图15. 人源化的单域抗体▶ 特性二：先导抗体数量多通过三优万亿人源化单域抗体库子库筛选获得的单域抗体先导分子数量多。通过14个不同靶点对ST-SDAL进行筛选验证，如图16所示，共获得9423个具有独特序列的人源化抗体克隆，所得克隆数中位值是606个。▲ 图16. 项目的抗体数量统计▶ 特性三：先导抗体亲和力高通过三优万亿人源化单域抗体库子库筛选获得的单域抗体候选分子具有较好的亲和活性。所获得抗体的亲和力可以达到nM。如图17为构建全长后的分子亲和力分析，结果显示大部分抗体克隆都有较好的亲和力。▲ 图17. 分子亲和力分析统计代表案例：抗新冠Spike蛋白单域抗体开发01背景新冠病毒Spike蛋白由3个相同的单体构成，其单体由S1亚基和S2亚基组成，S1亚基结构域包括NTD和RBD，S2亚基结构域包括FP、HR1、HR2、TM和CP。新型冠状病毒通过刺突蛋白(S蛋白)与宿主细胞上的受体血管紧张素转换酶Ⅱ (angiotensin converting enzyme Ⅱ，也称为ACE2)结合，介导病毒进入宿主细胞。新冠主流变异株包括Alpha、Belta、Delta，以及Omicron，使得已获批紧急使用的大部分中和抗体已失效。因此，开发结合表位的氨基酸序列相对保守、且具有较好中和效果的抗体极为重要。全球共有17个新冠相关的治疗型抗体上市或处于临床后期。阿斯利康（AstraZeneca）长效新冠病毒中和抗体Evusheld（AZD7442）已获美国FDA紧急使用授权（EUA）。Evusheld是两种长效单克隆抗体的组合新冠肺炎抗体（150 mg tixagevimab和150 mg cilgavimab）。我国首个具有自主知识产权的新冠中和抗体联合治疗药物由腾盛华创医药技术（北京）有限公司开发，由安巴韦单抗注射液（BRII-196）和罗米司韦单抗注射液（BRII-198）组成。RBD特异性的单抗能够结合Spike蛋白上RBD结构域里的RBM基序（receptor-binding motif）。RBM负责病毒与宿主细胞ACE2的初步结合，起始病毒进入细胞。RBD特异性单抗可以阻断RBM—ACE2的相互作用，是ACE2的阻断剂。02抗Spike抗体关键结果A 亲和活性检测：通过ELISA检测候选抗体与SARS-CoV-2突变株Omicorn S蛋白的结合活性。亲和活性实验结果如图18所示，候选抗体S1D-Ab-092和SID-Ab-102与SARS-CoV-2突变株Omicorn S蛋白的结合活性与对照抗体相当。▲ 图18. 抗体亲和力检测B 阻断活性分析：采用ELISA方法检测候选抗体对SARS-CoV-2 S蛋白与受体ACE2结合的阻断活性。结果如图19所示。候选抗体S1D-Ab-092和S1D-Ab-102都能有效阻断SARS-CoV-2 S蛋白与受体ACE2的结合。▲ 图19. 抗体阻断试验C 假病毒中和：通过荧光素酶报告系统检测S1D-Ab-102和对照抗体Sotrovimab中和Omicron假病毒的活性，结果如图20所示，S1D-Ab-102中和的IC50值与阳性对照相当，但完全抑制率优于阳性对照。▲ 图20. 假病毒中和05 千亿级高等电点单域抗体发现平台01平台概览三优千亿级高等点单域抗体库，采用先进的AI引物设计技术，在精准维持高等电点的同时，剔除了翻译后修饰位点，显著提高了单域抗体的成药性，加速了单域抗体药物的开发进程（如图21所示）。该文库库容高达1.00千亿，拥有独立知识产权，并匹配了全面的理化及生化分析进行筛选。▲ 图21. 千亿级高等点单域抗体库02平台经验三优千亿级高等点单域抗体库仅需5-6周即可获得特异性好、亲和力高、序列明确并经真核表达验证的单克隆抗体。与传统单域抗体相比，千亿级高等点单域抗体库显著提高了分子等电点，排除了PTM位点，成药性大幅提升。千亿级高等点单域抗体库针对不同难度的靶点，平均可获得35个序列独特、特异性好、成药性高的先导抗体（如图22所示）。▲ 图22. 针对不同难度的靶点获得的先导抗体统计03服务特性▶ 特性一：抗体先导分子等电点高通过对人源化单域抗体库筛选测序，序列分析结果表明，等电点（pI）在8.0-9.0范围内的分子占比显著提高，如图23所示。高等电点能够改善溶解度、降低聚集倾向，并增强在体内的稳定性，从而显著提升候选药物的生物利用度和药代动力学特性。此外，该等电点范围内的分子通常表现出更低的非特异性结合，减少了潜在的脱靶效应，进一步提高了药物的安全性和有效性。▲ 图23. 单域抗体库等电点分子比较▶ 特性二：抗体先导分子无PTM位点通过对千亿级高等点单域抗体库筛选测序，序列分析结果表明，候选分子不含翻译后修饰（PTM）位点（如图24所示）。PTM位点的缺失意味着这些分子具有更高的结构稳定性、更低的免疫原性和更长的体内半衰期，从而显著提升了其成药性。此外，无PTM位点也降低了生产过程中出现异质性的风险，简化了纯化和质量控制流程。▲ 图24. 单域抗体库分子翻译修饰后特点06 案例统计截止目前，三优生物已完成500+单域抗体库的筛选验证，通过三优单域抗体库筛选获得的单域抗体候选分子具有较好的亲和活性。经过十年的努力与积累，三优生物形成了一个在创新分子库领域持续发展和迭代创新的专业化研发团队，积累了大量的关于分子库的工程设计知识和经验，形成了一系列核心技术的积累，在“超万亿分子库”方面已经奠定了坚实的基础。在授权转让或合作开发的9个IND项目中，有5个项目运用了三优生物单域抗体开发平台，目前已经获得了IND批件或推进至临床开发阶段（如表5所示）。▼ 表5. 单域抗体库相关案例统计代表案例：抗CLDN18.2单域抗体开发01背景CLDN18.2是构成紧密连接结构的一种膜蛋白，具有四次跨膜结构；其两个剪切变体CLDN18.1和CLDN18.2的氨基酸序列一致性高达91%。临床研究数据显示，70%的胃癌患者高表达CLDN18.2，且预后较差；CLDN18.2仅特异性表达于胃上皮细胞，其他健康组织中不表达。因此，开发特异性识别CLDN18.2的抗体药物，有望为胃癌患者提供精准安全的治疗。目前仅有一款针对CLDN18.2的抗体药物物处于三期临床，即IMAB362；其与紫杉醇联合用药的二期临床数据显示，CLDN18.2过表达的胃食管癌病人用药后的总生存期从9个月提升到16.7个月。抗CLDN18.2单克隆抗体与肿瘤细胞表面的CLDN18.2结合，以刺激激活抗体依赖性细胞毒性(ADCC)和补体依赖性细胞毒性(CDC)的细胞和可溶性免疫效应物。此外，抗CLDN18.2单克隆抗体还可以诱导细胞凋亡和抑制细胞增殖。02CLDN18.2抗体关键结果▶ 细胞水平的结合活性分析：通过三优万亿人源化单域抗体库子库筛选获得的单域抗体候选分子候选分子大多具有较好的细胞水平结合活性。如图25展示了采用FACS分析候选抗体与Human CLDN18.2-HEK293T细胞的亲和力测定结果，其中全部候选抗体的亲和力水平优于对照抗体。▲ 图25. 通过FACS进行结合亲和力测定▶ 体外药效验证：A ADCC和CDC分析：候选抗体由于包含有IgG1 Fc片段，可以通过抗体依赖的细胞毒性效应（ADCC）和补体依赖的细胞毒性效应（CDC）对靶细胞进行杀伤。如图所示，候选抗体 C2 对 Human CLDN18.2-HEK293T细胞的ADCC杀伤效果与对照抗体相当；如图26所示,候选抗体C2对Human CLDN18.2-HEK293T细胞的CDC杀伤效果与对照抗体相当。▲ 图26. 通过FACS进行ADCC与CDC测定B 内吞作用分析：内吞作用是指膜表面抗原与抗体结合之后将抗体吞至细胞内部的过程。如图27展示的是anti-CLDN18.2抗体介导的内吞作用将毒素递送入细胞后的毒性分析。结果显示，候选抗体C2可介导毒素对Human CLDN18.2-HEK293T的杀伤，且效果优于对照抗体。内吞作用结果指示候选抗体C2有可能用于ADC抗体药物的开发。▲ 图27. 人源CLDN18.2-HEK293T细胞内化检测C 体内药效验证：通过三优万亿人源化单域抗体库子库筛选获得的单域抗体候选分子体内药效优秀，甚至优于对照抗体。免疫检查点A的候选分子在MC38人源化小鼠模型的体内抗肿瘤药效验证案例如图28所示。在人源化小鼠皮下接种MC38细胞，接种6天后开始进行药物治疗，治疗方式为腹膜内注射方式给药，每周两次，连续给药三周。结果显示：候选抗体(C2)在0.4 MPK剂量时可完全抑制肿瘤生长，显示出了极其优异的抗肿瘤效果。▲ 图28. 肿瘤生长抑制07 总结展望单域抗体凭借其在肿瘤靶向治疗、免疫治疗以及抗病毒药物研发等领域的广泛应用，展现出强劲的市场增长潜力。据预测，全球单域抗体市场将以15%-20%的复合年增长率快速扩张，预计到2030年市场规模将达到50亿至100亿美元。为加速单域抗体药物的研发进程，三优生物精心打造了三大核心技术平台：羊驼免疫抗体发现平台、人源化单域抗体开发平台及高等电点单域抗体筛选平台。这些平台可全面覆盖多种靶点类型，能够高效获得先导分子。展望未来，三优生物将在单域抗体研发领域持续深耕，通过双轮驱动策略推动创新突破。一方面，公司将在现有高等电点单域抗体库的基础上，进一步扩大库容，为药物筛选提供更丰富的分子资源；另一方面，将深度融合人工智能技术，打造智能化抗体研发平台，重点开发抗体从头设计，全面提升药物开发效率与成功率，为创新生物药的研发注入强劲动力。推荐阅读三优生物双抗参比品网站SY-BsAb正式上线三优ADC药物研发系统解决方案三优生物oneClick+平台再次上新三优磁阵列全人源小鼠抗体发现平台重磅发布三优超万亿全人单克隆抗体产生平台盘点三优磁阵列全人源小鼠抗体发现平台隆重上线共同轻链抗体产生之超万亿共轻库盘点三优生物73种全系列双抗参比品全新上线三优生物智能超万亿分子发现平台盘点及展望十年磨一剑之三优智能百万亿分子库发展历程三优生物2024｜夯基筑本AI-STAL 1.0超实用！你不容错过的oneClick+ AI在线小程序重磅发布｜三优生物云试剂管家正式上线三优Mrna Mab创新抗体产生技术平台重磅发布破除新药之内卷利剑｜超万亿分子库的前世今生关于三优生物三优生物是一家以“运用创新生物药提高人类的生活品质”为愿景，以“让天下没有难做的创新生物药”为使命的生物医药高新技术企业。公司总部位于中国上海，在美国、欧洲等地设有子公司，现有投产及布局的研发及GMP场地20000多平方米。公司以智能超万亿分子库为核心，打造了国际领先的创新生物药临床前智能化及一体化研发平台，通过“新药发现、临床前研究、智能化药物研发及前沿科学研究”等四个维度加速创新生物药物的研发进程。公司为合作伙伴提供“差异化CRO、整合型CDO、协同型CPO、特色CRS”于一体的“创新生物药4C综合业务”。公司已建立全球营销网络，已与全球1200多家药企、生技公司等建立了良好的合作关系；已完成了1200多个新药发现及开发服务项目；已完成了50多个合作研发项目，其中9个合作项目已完成临床申报；公司开发了数千种品牌试剂。公司已获得国家高新技术、上海市专精特新、上海市小巨人和上海“张江之星”企业认定。

免疫疗法临床申请

2025-04-08

·astrazeneca.com

AstraZeneca showcases innovation in infectious disease protection at ESCMID Global 2025

AstraZeneca will share new data across its Vaccines & Immune Therapies portfolio at the 2025 Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global 2025) in Vienna, Austria, from 11-15 April 2025. With 13 abstracts, including two oral presentations and two late-breaking poster presentations, the Company will highlight progress in advancing novel immunisations against bacterial and viral infectious diseases and share real-world evidence showing the burden of respiratory viral infections and the continued need for protection. Benjamin Moutier, Senior Vice President, Vaccines & Immune Therapies, AstraZeneca said: “AstraZeneca is building an innovative portfolio of antibodies and vaccines to tackle two of the top global public health threats – serious bacterial infections and respiratory viral infections. At ESCMID, we’ll share data on three novel monoclonal antibodies targeting high-priority pathogens, highlighting our ambition to redefine care for serious bacterial infections. In addition, we will present 20 years of effectiveness data for Fluenz/FluMist, as well as real-world data highlighting the ongoing burden of RSV and hMPV, two leading causes of respiratory illnesses.” Advancing potential new options for serious bacterial infection prevention and treatment Serious bacterial infections pose significant and growing threats to global health, linked to an estimated 7.7 million deaths a year globally, leading to increasing morbidity and mortality for patients and a substantial burden on health systems.1 At ESCMID, the Company will share preclinical data on investigational monoclonal antibodies (mAbs) targeting three of the top five pathogens identified as urgent risks by the Centers for Disease Control and Prevention: Staphylococcus aureus (S. aureus): Oral presentation on in vivo expression of an mRNA-encoded multi-mechanistic mAb combination against S. aureus. There are millions of methicillin-resistant S. aureus (MRSA) infections annually worldwide, and MRSA is resistant to many types of antibiotics, making treatment highly complex. A pathogen-specific treatment strategy with mAbs targeting some S. aureus virulence factors represents an alternative to broad spectrum antibiotics.2 Pseudomonas aeruginosa (P. aeruginosa): Preclinical data showing that gremubamab, an anti-P. aeruginosa bispecific human mAb, may enhance neutrophil-mediated killing of P. aeruginosa in bronchiectasis patients. P. aeruginosa is a pathogen that colonizes one-third of patients with bronchiectasis, a chronic lung condition impacting about one million people globally and drives significant disease morbidity and mortality.3 Klebsiella pneumoniae (K. pneumoniae): Research on the development and characterisation of bispecific antibodies that protect against bacteraemia and pneumonia from the major serotypes of antibiotic-resistant K. pneumoniae in mouse models. Infections caused by K. pneumoniae are responsible for more than 700,000 yearly deaths worldwide.4 Real-world data examining the impact of respiratory infections AstraZeneca is presenting 20 years of real-world data on Fluenz/FluMist (live attenuated influenza vaccines, LAIV), recently approved in the U.S. as the only vaccine for self- or caregiver administration for the prevention of influenza, demonstrating long-term effectiveness comparable to that of inactivated (IIV) influenza vaccines in children.5 The Company will also present two late-breaking posters featuring real-world studies in patients with haematological malignancies who are highly susceptible to severe respiratory infections. The studies show that outcomes from human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) were similar to those from influenza and COVID-19, highlighting the need for development of novel options for preventing disease caused by hMPV and RSV.6,7 Retrospective analyses from Valencia, Spain, where there is systematic testing for multiple respiratory viruses, highlight the impact of RSV and influenza on severe disease and mortality in older adults throughout the COVID-19 pandemic, and suggest a potentially greater proportion of mechanical ventilation use and in-hospital death from RSV than influenza in adolescents and adults.8,9 Additional real-world data from France highlight the extensive healthcare resource utilisation due to hMPV and RSV and underline the need for routine testing for hMPV to accurately assess its true burden.10 Additionally, data being presented by our partner, Sanofi, confirm the significant public health impact and real-world effectiveness of Beyfortus in reducing RSV disease and hospitalisations in infants.11 Furthering Research in COVID-19 Prevention Data on AZD6563, an investigational novel COVID-19 mRNA vaccine-like particle (VLP) vaccine, demonstrating that a low dose may elicit equivalent cell-mediated immunity to a licensed mRNA vaccine will also be shared.12 Additionally, data will be presented increasing confidence in a SARS-CoV-2 variant-agnostic threshold which could be used as a surrogate endpoint for benchmarking expected efficacy of novel mAbs for the prevention of COVID-19 against emerging variants.13 Key AstraZeneca presentations during ESCMID 2025 Abstract Title Presentation Details Abstract Title Early Science: Serious Bacterial Infections and Respiratory Viral Infections Abstract Title In vivo expression of an mRNA encoded multi-mechanistic mAb combination against Staphylococcus aureus and protection in disease model Presentation Details Oral Presentation Session Title: Around the Lab in 80 Ways: A Journey Through Innovative Therapeutics Date: Saturday 12 April 2025 Time: 11 AM – 12 PM CEST Location: Hall 13 Abstract Title Low dose of a novel SARS-COV-2 mRNA VLP vaccine elicits equivalent cell-mediated immunity to a licensed mRNA vaccine Presentation Details Poster Presentation Session Title: COVID-19 Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Bronchiectasis Patient Neutrophil-Mediated Killing Of Pseudomonas aeruginosa Presentation Details Poster Presentation Session Title: Drug Discovery and New Compounds Mechanisms of Action & Spectrum, Preclinical Data & Basic Pharmacology Date: Sunday 13 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Broad coverage of antibiotic-resistant Klebsiella pneumoniae by multi-specific antibodies against the lipopolysaccharide O-antigen Presentation Details Poster Presentation Session Title: Drug Discovery and New Compounds Mechanisms of Action & Spectrum, Preclinical Data & Basic Pharmacology Date: Sunday 13 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Real-World Evidence: Respiratory Infections Abstract Title Comparative outcomes of hMPV, influenza, and SARS-CoV-2 infections in haematologic malignancy patients: A matched cohort analysis Presentation Details Late-Breaking Poster Presentation Session Title: Outbreaks and Public Health Emergencies Date: Tuesday 15 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Matched cohort study comparing the impact of RSV, influenza, and SARS-CoV-2 infections in patients with haematological malignancies Presentation Details Late-Breaking Poster Presentation Session Title: Outbreaks and Public Health Emergencies Date: Tuesday 15 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Similar proportions and temporal patterns of influenza, RSV, and hMPV among ESKD patients tested between 2020-2023 Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Characterization of hMPV and RSV cases in the French national hospital claims database during the 2022-2023 season Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Shifting viral landscapes: the impact of SARS-CoV-2 on hospitalization, ICU admission, and mortality in respiratory infections among older adults in Valencia, Spain Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Respiratory syncytial virus (RSV)-associated hospitalised influenza-like illness (ILI) and clinical progression in adolescents and adults in Valencia, Spain, 2014/2015-2019/2020: the VALSARI study Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title Real-world effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines in children: a systematic literature review (SLR) and network meta-analysis (NMA) Presentation Details Poster Presentation Session Title: Influenza and Respiratory Viruses Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Abstract Title COVID-19 mAbs Abstract Title Pharmacokinetics and immunogenicity of AZD7442 (Tixagevimab/Cilgavimab) in hospitalised COVID-19 patients: results from the DisCoVeRy trial Presentation Details Oral Presentation Session Title: New developments in prophylaxis and treatment of COVID-19 Date: Saturday 12 April 2025 Time: 11:00 Location: Hall 6 Abstract Title A threshold of protection model for monoclonal antibody pre-exposure prophylaxis against COVID-19 enabling rapid development for future SARS-CoV-2 variants Presentation Details Poster Presentation Session Title: COVID-19 Date: Saturday 12 April 2025 Time: 12 PM – 1:30 PM CEST Location: Poster Area in Hall D Notes AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References 1. GBD 2019 Antimicrobial Resistance Collaborators. Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022 Dec 17;400(10369):2221-2248. 2. Tkaczyk C, Newton M et al. In vivo expression of an mRNA encoded multi-mechanistic mAb combination against Staphylococcus aureus and protection in disease model. Oral Presentation. ESCMID Global 2025; Vienna, Austria. 2025. 3. Long MB, Gilmour A et al. A bispecific monoclonal antibody targeting Psl and PcrV enhances bronchiectasis patient neutrophil-mediated killing of Pseudomonas aeruginosa. Poster Presentation #P3642. ESCMID Global 2025; Vienna, Austria. 2025. 4. Doyle M, Smith A et al. Broad coverage of antibiotic-resistant Klebsiella pneumoniae by multi-specific antibodies against the lipopolysaccharide O-antigen. Poster Presentation #P2377. ESCMID Global 2025; Vienna, Austria. 2025. 5. Stuurman AL, Enxing J et al. Real-world effectiveness of live attenuated (LAIV) and inactivated (IIV) influenza vaccines in children: a systematic literature review (SLR) and network meta-analysis (NMA). Poster Presentation #P0120. ESCMID Global 2025; Vienna, Austria. 2025. 6. Salmanton-Garcia J, Marchesi F et al. Comparative outcomes of hMPV, influenza, and SARS-CoV-2 infections in haematologic malignancy patients: a matched cohort analysis. Poster Presentation #P5067. ESCMID Global 2025; Vienna, Austria. 2025. 7. Marchesi F, Salmanton-Garcia J et al. Matched cohort study comparing the impact of RSV, influenza, and SARS-CoV-2 infections in patients with haematologic malignancies. Poster Presentation #P5066. ESCMID Global 2025; Vienna, Austria. 2025. 8. Mira-Iglesias A, Herring T et al. Respiratory syncytial virus (RSV)-associated hospitalisations and clinical progression in adolescents and adults in Valencia, Spain, 2014/2015–2019/2020: the VALSARI study. Poster Presentation #P0131. ESCMID Global 2025; Vienna, Austria. 2025. 9. Mira-Iglesias A, Herring T et al. Respiratory syncytial virus (RSV)-associated hospitalisations and clinical progression in adolescents and adults in Valencia, Spain, 2014/2015–2019/2020: the VALSARI study. Poster Presentation #P0132. ESCMID Global 2025; Vienna, Austria. 2025. 10. Binh Luong Nguyen L, et al. Characterisation of hMPV and RSV hospitalisations in the French national hospital claims database during the 2022-2023 season. Poster Presentation #P0183. ESCMID Global 2025; Vienna, Austria. 2025. 11. Mallah N, Pardo-Seco J, et al. Effectiveness of universal prophylaxis with nirsevimab for prevention of infant hospitalisations due to respiratory syncytial virus : full 2023-24 season analysis of the NIRSE-GAL study. Poster Presentation #P0124. ESCMID Global 2025; Vienna, Austria. 2025. 12. Swanson PA II, Padilla M et al. Low dosage of a novel SARS-COV-2 mRNA VLP vaccine elicits equivalent cell-mediated immunity to a licensed mRNA vaccine. Poster Presentation # P0482. ESCMID Global 2025; Vienna, Austria. 2025. 13. Edge R, Matthews S et al. A validated threshold of protection model for monoclonal antibody pre-exposure prophylaxis against COVID-19 enabling rapid development for future SARS-CoV-2 variants. Poster Presentation #P0448. ESCMID Global 2025; Vienna, Austria. 2025. Corporate and financial

疫苗上市批准免疫疗法临床研究信使RNA

2025-03-14

·PipelineReview

INOVIO Announces Promising Interim Results from Ongoing Proof-of-Concept Clinical Trial of DNA-Encoded Monoclonal Antibodies (DMAbs) for COVID-19

PLYMOUTH MEETING, PA, USA I March 13, 2025 I INOVIO (NASDAQ: INO ), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced promising interim results from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs for COVID-19. In the trial, 100% (24/24) of participants who have reached week 72 maintained biologically relevant levels of DMAbs, confirming the durability of in vivo antibody production. Notably, no participant developed anti-drug antibodies (ADA), a common challenge observed in other gene-based delivery platforms, such as adeno-associated virus (AAV) mediated antibody expression. Additionally, the DMAbs were well tolerated, with the most common side effects being mild, temporary injection site reactions, such as pain and redness. The trial is being led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and clinical investigators at the Perelman School of Medicine at the University of Pennsylvania. “This study provides the first clinical proof-of-concept that DNA-encoded monoclonal antibodies can be durably and tolerably expressed in humans,” said David B. Weiner, Ph.D, Executive Vice President of The Wistar Institute and lead investigator for the study. “These findings could represent a breakthrough as they demonstrate the potential of DMAb technology to overcome traditional monoclonal antibody production challenges, such as short half-life and anti-drug immune responses, making it a promising platform for a broad range of diseases. This technology has the potential to transform treatments for infectious diseases, as well as cancer and metabolic disorders by enabling long-term expression of therapeutic antibodies and other proteins.” “One of the biggest hurdles for gene-based antibody delivery has been the immune system’s response to the vector or the antibody itself, leading to anti-drug antibodies that can limit how long a treatment will be effective,” said Pablo Tebas, M.D., a professor of Infectious Diseases at Penn. “Our DNA-based approach has demonstrated sustained antibody expression without generating ADA. And because antibodies are remaining active for longer, our approach may be a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery.” INOVIO’s Chief Scientific Officer, Laurent Humeau, Ph.D. added: “We believe these data highlight the potential to apply our DNA Medicines technology to deliver a broad spectrum of therapeutic proteins that could be used to treat diseases with missing or defective proteins. We’d like to thank our partners in advancing this important new technology and we look forward to working with them to complete this trial and on future research where we anticipate exploring broader applications of our technology for long-term therapeutic protein delivery.” A manuscript describing interim results from the trial has been uploaded to Research Square for early dissemination and is under peer review by a leading scientific journal for publication. The consortium plans to present interim results from the trial at upcoming scientific conferences in 2025. About the Phase 1 Trial The Phase 1 trial is the first clinical study to report using synthetic DNA technology to enable in vivo production of monoclonal antibodies directly from muscle cells. Participants received an intramuscular (IM) injection of synthetic DNA plasmids encoding AZD5396 and AZD8076 (derived from AstraZeneca’s cilgavimab and tixagevimab) delivered via INOVIO’s proprietary CELLECTRA 2000 electroporation (EP) device. This delivery method temporarily increases cell permeability, which is intended to facilitate efficient DNA uptake and enable sustained antibody production. The study is an open-label, single center, dose-escalation trial. Enrollment began in May 2022 and was completed in March 2024. The most common side effects observed were temporary local injection site reactions, such as pain and erythema, associated with the administration of the study product. There were three SAEs all of which were considered unrelated to the study product. Now in its third year, the trial is led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and clinical investigators at the University of Pennsylvania. It is funded by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) and the Defense Advanced Research Projects Agency (DARPA). About INOVIO’s DNA Medicines Platform INOVIO’s DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO’s proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software that the body’s cells can download to produce specific proteins to target and fight disease. INOVIO’s proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body’s cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms. About INOVIO INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO’s technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com . SOURCE: INOVIO Pharmaceuticals

临床1期临床结果

100 项与替沙格韦单抗相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床1期	美国	AstraZeneca PLC	2022-05-19

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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


EULAR2024	N/A	新型冠状病毒感染 \| 胶原蛋白疾病	90	Tixagevimab and Cilgavimab (Evusheld)	醖網觸顧鏇選窪選簾鏇(齋襯網獵壓願範齋壓範) = 蓋製壓窪壓鹽餘鑰簾簾糧簾醖夢願膚範鏇築鏇 (膚獵顧齋願膚夢鹹憲選 )	积极	2024-06-05
				Tixagevimab (Control group (not treated with EVS))	醖網觸顧鏇選窪選簾鏇(齋襯網獵壓願範齋壓範) = 構鏇鏇選鏇範鏇範衊築糧簾醖夢願膚範鏇築鏇 (膚獵顧齋願膚夢鹹憲選 )
AAN2024	N/A	视神经脊髓炎 \| 多发性硬化症	-	Tixagevimab/Cilgavimab (T/C)	窪鹽餘廠顧觸顧憲範顧(繭齋齋衊簾鑰廠構蓋選): median relative risk = 7.6 (95% CI, 0.02 ~ 115.9), P-Value = 0.242	-	2024-04-09
				Tixagevimab/Cilgavimab (Evusheld) (Control Group (CG))
ECTRIMS2023	N/A	多发性硬化症 anti-CD20 monoclonal antibodies	-	Evusheld	鹽鑰壓壓襯齋觸鑰壓觸(淵製襯獵獵壓製鏇鹽窪) = Solely four patients (2.08%) developed SARS-CoV-2 infection after Evusheld treatment, presenting with a mild (75%) or moderate (25%) illness. No medical admission was recorded. 艱範鹽範憲壓築鏇膚艱 (鬱襯窪繭窪艱製壓鏇醖 ) 更多	积极	2023-09-30
EULAR2023	N/A	胶原蛋白疾病	21	Tixagevimab and Cilgavimab (TGM/CGM)	廠構壓鑰鬱襯遞膚壓觸(憲範積齋膚夢憲醖鏇壓) = no COVID-19 related symptoms were observed in the month of follow-up after TGM/CGM administration 壓繭襯壓蓋醖製願鬱膚 (鹽蓋齋醖窪簾襯鏇獵襯 ) 更多	-	2023-05-31
ACTRIMS2023	N/A	新型冠状病毒感染	-	Evusheld 150mg	壓壓積鏇夢壓顧範淵夢(鬱築範獵鏇選製顧選鹹) = All patients had grade 1 or 2 (mild) severity of COVID-19 觸醖糧獵憲鑰蓋鑰繭壓 (鬱襯鹽窪廠鏇淵願積鹽 ) 更多	积极	2023-05-30
				Evusheld 300mg
ATS2023	N/A	移植肺并发症	-	Tixagevimab and Cilgavimab (Evusheld)	蓋網窪製鏇淵獵廠鹹窪(鏇膚網淵蓋繭襯餘餘襯) = 壓製醖範壓餘製窪網願衊獵蓋餘繭築願築構齋 (遞選壓築選鹹餘艱夢鑰, 9.4% ~ 33.9%) 更多	-	2023-05-21
AAAAI2023	N/A	新型冠状病毒感染	55	Evusheld	鑰鹽範繭鹹鏇鑰鏇糧鏇(膚製網範壓醖壓觸餘積) = all were prescribed oral antivirals 淵窪築鹽蓋鏇積醖繭鑰 (廠鹽網餘構窪憲鹹觸壓 ) 更多	积极	2023-02-01
ACAAI2022	N/A	原发性免疫缺陷疾病	79	Tixagevimab and Cilgavimab	顧蓋衊淵構淵膚選願選(襯窪願窪鏇繭願憲顧壓) = 鏇蓋獵壓醖蓋範襯廠遞膚夢觸鹹築醖蓋憲構獵 (糧鏇觸醖顧鹽築壓艱鑰 )	不佳	2022-11-10
				No Tixagevimab and Cilgavimab	顧蓋衊淵構淵膚選願選(襯窪願窪鏇繭願憲顧壓) = 獵積艱憲網遞糧窪蓋夢膚夢觸鹹築醖蓋憲構獵 (糧鏇觸醖顧鹽築壓艱鑰 )