A Phase 2 Study of VB119 in Adult Subjects With Steroid-Sensitive Primary Minimal Change Disease (MCD) or Primary Focal Segmental Glomerulosclerosis (FSGS)

Phase 2, multi-center, proof-of-concept study to evaluate the safety and efficacy of VB119 on the maintenance of remission and duration of response in adults with primary MCD or primary FSGS who previously responded to steroid therapy.

开始日期2022-05-03

申办/合作机构-

NCT04652570 / Active, not recruiting临床1/2期

A Phase 1b/2a Study of VB119 in Adult Subjects With Primary Membranous Nephropathy

This study is a Phase 1b/2a, open-label, sequential-cohort, dose escalation, and dose expansion study to evaluate the safety, tolerability, PK, and PD of VB119 in subjects with primary MN

开始日期2021-05-05

申办/合作机构-

100 项与 VB-119 相关的临床结果

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100 项与 VB-119 相关的转化医学

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100 项与 VB-119 相关的专利（医药）

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项与 VB-119 相关的文献（医药）

2018-06-14·Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

[Construction and in vitro verification of a new humanized anti-CD19 CAR-T cells with high affinity].

Article

作者: Qi, K M ; Wu, Q Y ; Chen, W ; Zhang, C X ; Xu, K L ; Cheng, H ; Cao, J ; Han, X

Objective: To construct humanized anti-CD19 chimeric antigen receptor T cells and investigate its ability to kill leukemia cells in vitro and in vivo. Methods: Humanized anti-human CD19 antibody with a high affinity was obtained based on mouse anti-human CD19 antibody (FMC63). Humanized CD19 CAR-T cells (hCART19) were constructed through transfection of lentivirus carrying a CAR sequence of humanized anti-CD19 scFv into human peripheral CD3(+) T cells. The ability of hCART19 to kill leukemia cells and secrete cytokines was detected by LDH release assay and ELISA. The in vivo tumor-killing effect of hCART19 was evaluated in a leukemia mouse model. Results: Several different humanized CD19 single-chain antibodies which were constructed by IMGT database were expressed in the eukaryotic expression vector and purified followed by acquiring humanized CD19 antibody (Clone H3L2) with similar binding ability to FMC63. Humanized CD19 CAR lentivirus vector was constructed and transfected into T cells to obtain hCART19 cells. The LDH release experiment confirmed that the killing rate of target cells was increased gradually along with the increased E/T ratio. When the ratio of E/T was 10∶1, the killing rate of target cells by hCART19 reached a maximum. When Raji cells were used as target cells, the hCART19 cells group had a significantly higher kill rate [(87.56±1.99)%] than the untransduced T cells group [(19.31±1.16)%] and the control virus transduced T cells group [(21.35±1.19)%](P<0.001). ELISA analysis showed that the secretion of IL-2 [ (10.56±0.88) pg/ml] and IFN-γ [ (199.02±12.66) pg/ml] in the hCART19 cells group were significantly higher than those in the untransduced T cells group [IL-2: (3.55±0.26) pg/ml; IFN-γ: (37.63±0.85) pg/ml] and the control virus transduced T cells group [IL-2: (2.92±0.32) pg/ml; IFN-γ: (52.07±3.33) pg/ml](P<0.001). The above experiments also showed similar results when CHO-K1-CD19 cells were used as target cells. Moreover, in a human leukemia xenograft animal model, the results showed that mice in the untransduced T cells group and the control virus transduced T cells group all died within 20 to 30 days, and the hCART19 cell group survived >40 days, which was more than the survival time of the other two groups of mice. The difference was statistically significant (χ(2)=11.73, P=0.008). Conclusion: Humanized CD19 CAR-T cells with anti-leukemic activity have been successfully constructed, which will lay a foundation for clinical studies in the future.

Cancer management and research3区 · 医学

Targeting CD19 in B-cell lymphoma: emerging role of SAR3419

3区 · 医学

ReviewOA

作者: Abdul Shukkur Ebrahim ; Ali Raufi ; Ayad Al-Katib

Non-Hodgkin lymphoma symbolizes a heterogeneous group of diseases resulting from malignant transformation of lymphocytes with differing patterns of behavior and responses to treatment. The potential curability of non-Hodgkin lymphoma differs among the various histologic subtypes and is associated in part with the stage at presentation. CD19 antigen is a type I transmembrane glycoprotein belonging to the immunoglobulin Ig superfamily. CD19 is specifically expressed in normal and neoplastic B-cells. Recent study showed that in a mouse model, CD19 and c-Myc synergize functionally to accelerate B-cell lymphomagenesis, which is associated with increased disease severity. Specificity is the most important challenge in cancer therapeutics. Antibody-drug conjugates have the prospect of enhancing the therapeutic efficacy over unconjugated monoclonal antibodies through the selective delivery of cytotoxic agents to cancer cells. The ubiquitous expression of CD19 in these tumors, especially at an earlier stage and the property of efficient internalization, makes CD19 an attractive and affective target for antibody-drug conjugate therapy as compared to CD20. SAR3419 (huB4-DM4) is a novel antibody-drug conjugate that is composed of a humanized monoclonal IgG1 anti-CD19 antibody (huB4) attached to the potent cytotoxic drug, a maytansine derivative (DM4), through a cleavable disulfide cross-linking agent N-Succinimidyl-4-2-pyridyldithio butanoic acid (SPDB). The preclinical efficacy of maytansine derivative-anti-CD19 conjugate was demonstrated in our laboratory, and SAR3419 was found to be more effective than CHOP in a xenograft model. Phase I trials have also been conducted on the basis of preclinical studies that demonstrated promising antitumor activity with acceptable safety results in human B-cell lymphoma models. Additional trials are ongoing and will provide additional insight into the full potential of this novel drug.

项与 VB-119 相关的新闻（医药）

2023-06-01

·PRNewswire

Idiopathic Membranous Nephropathy Market to Register Immense Growth at a CAGR of 12% During the Study Period (2019-2032), Predicts DelveInsight

As potential therapies are being investigated to manage idiopathic membranous nephropathy, it is safe to predict that the idiopathic membranous nephropathy market will experience significant reconstitution during 2023–2032. However, the challenges of the rigid and burdensome structure of regulatory authorities will decide the fate of all these pipeline therapies and the impact they will have on overall revenue generation. LAS VEGAS, June 1, 2023 /PRNewswire/ -- DelveInsight's Idiopathic Membranous Nephropathy Market Insights report includes a comprehensive understanding of current treatment practices, idiopathic membranous nephropathy emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan] and China. Key Takeaways from the Idiopathic Membranous Nephropathy Market Report As per DelveInsight analysis, the idiopathic membranous nephropathy market size in the 7MM + China was approximately USD 220 million in 2022. According to the assessment done by DelveInsight, the estimated total prevalent idiopathic membranous nephropathy cases in the 7MM + China were approximately 380K in 2022. Leading idiopathic membranous nephropathy companies such as Hoffmann-La Roche, MorphoSys, Cerium Pharmaceuticals, BeiGene, Reistone Biopharma, Eternity Bioscience, GlaxoSmithKline, ValenzaBio, ACELYRIN, and others are developing novel Idiopathic Membranous Nephropathy drugs that can be available in the Idiopathic Membranous Nephropathy market in the coming years. The promising idiopathic membranous nephropathy therapies in the pipeline include GAZYVA (obinutuzumab), MOR202 (felzartamab), SNP-ACTH (1-39) Gel, BRUKINSA (zanubrutinib), SHR1459 (edralbrutinib), BENLYSTA (belimumab), VB119 , and others. Discover which therapies are expected to grab the major idiopathic membranous nephropathy market share @ Idiopathic Membranous Nephropathy Market Report Idiopathic Membranous Nephropathy Overview Membranous nephropathy is a kidney disease affecting the kidney's filters. It causes a rise in protein in the urine, impaired renal function, and edoema. It's also known as membranous glomerulopathy. Membranous nephropathy is a rare disease that affects the renal glomerulus, specifically the podocytes, which play an important role in limiting the permeability of the kidney to proteins. The most common membranous nephropathy symptom is swelling, often known as edema. This might range from minor to severe. Most patients have some edema, which is generally the initial symptom. Swelling in membranous nephropathy is usually slow compared to other disorders that cause protein in the urine and nephrotic syndrome, but it can sometimes be sudden. It usually begins in the feet, ankles, or legs, although it can develop elsewhere in the body, including the abdomen, hands, arms, and face. Protein in the urine is frequently used to make membranous nephropathy diagnosis. A blood test, a kidney biopsy, optical microscopy, immunofluorescence, electron microscopy, and antibody-guided diagnostics are also conducted. Idiopathic Membranous Nephropathy Epidemiology Segmentation DelveInsight estimates that there were approximately 380K prevalent cases of idiopathic membranous nephropathy in the 7MM in 2022. China contributed to the largest prevalent population of idiopathic membranous nephropathy, acquiring ~82% of the 7MM and China in 2022. Whereas EU4 and the UK for ~6%, and Japan accounted for ~ 5% of the total population share, in 2022. The idiopathic membranous nephropathy market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM + China segmented into: Idiopathic Membranous Nephropathy Prevalence Idiopathic Membranous Nephropathy Prevalence by Antigens Idiopathic Membranous Nephropathy Treatment Market There is no cure for either primary or secondary membranous nephropathy. When treating individuals with the illness, doctors usually take a symptomatic approach and aim to improve the patient's immune system. Patients are put on supportive care as soon as the diagnosis is confirmed, regardless of the underlying cause, and this is continued throughout the duration of the condition. It includes careful blood pressure control, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy to reduce proteinuria and increase the chances of spontaneous remission, statins for hyperlipidemia, salt restriction, diuretics to control edoema, and a low protein diet to allow for the replacement of urinary protein losses. In recent research, alkylating drugs used in combination with corticosteroids produced positive results in membranous nephropathy patients. Immunosuppressive therapy (such as steroids and alkylating agents, calcineurin inhibitors (CNIs), and rituximab) are among the medications used to treat membranous nephropathy patients. Alkylating drugs, steroids, and calcineurin inhibitors (CNIs) have formed the foundation of immunosuppression and immunosuppressive medications. Though they are partially effective in reducing proteinuria in membranous nephropathy patients, they have also been linked to greater relapse rates and significant adverse responses. To know more about idiopathic membranous nephropathy treatment guidelines, visit @ Idiopathic Membranous Nephropathy Management Idiopathic Membranous Nephropathy Pipeline Therapies and Key Companies GAZYVA (obinutuzumab): Hoffmann-La Roche MOR202 (felzartamab): MorphoSys SNP-ACTH (1-39) Gel: Cerium Pharmaceuticals BRUKINSA (zanubrutinib): BeiGene SHR1459 (edralbrutinib): Reistone Biopharma/Eternity Bioscience BENLYSTA (belimumab): GlaxoSmithKline VB119: ValenzaBio/ACELYRIN Learn more about the FDA-approved drugs for idiopathic membranous nephropathy @ Drugs for Idiopathic Membranous Nephropathy Treatment Idiopathic Membranous Nephropathy Market Dynamics The dynamics of the idiopathic membranous nephropathy market are expected to change in the coming years. Increased research activities and the discovery of new biomarkers and therapeutic targets, will result in the development of improved medicines in the future. Although rituximab is effective, patients can acquire medication resistance over time. Roche's Obinutuzumab is being developed with improved efficacy, which will aid in overcoming the limits of current therapy. Moreover, the rapid incidence of progression and remission in membranous nephropathy patients provides pharmaceutical companies with an opportunity to develop therapies to address the inadequacies and capture a largely untapped idiopathic membranous nephropathy market. Only a few drugs, such as Obinutuzumab, are in the latter stages of development. As a result, it opens the door for additional pharmaceutical companies to enter the idiopathic membranous nephropathy market with fresh therapeutic choices. However, several factors may impede the growth of the idiopathic membranous nephropathy market. Due to knowledge gaps and a lack of clarity about membranous nephropathy pathology, there is an urgent scarcity of large-scale clinical studies assessing therapy alternatives in membranous nephropathy. The outcomes of idiopathic membranous nephropathy treatment candidates that are in various stages of clinical development and are expected to be launched are not available. As a result, establishing the safety and efficacy of these medications is difficult. Moreover, as membranous nephropathy is a rare indication, it is often overshadowed by more common and fatal renal diseases, thereby influencing the whole research and development process. Almost 30% of membranous nephropathy cases develop into ESRD, yet the therapeutic landscape is devoid of recognized medicines, leading to a high fatality rate. Scope of the Idiopathic Membranous Nephropathy Market Report Therapeutic Assessment: Idiopathic Membranous Nephropathy current marketed and emerging therapies Idiopathic Membranous Nephropathy Market Dynamics: Attribute Analysis of Emerging Idiopathic Membranous Nephropathy Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Idiopathic Membranous Nephropathy Market Access and Reimbursement Discover more about idiopathic membranous nephropathy drugs in development @ Idiopathic Membranous Nephropathy Clinical Trials Table of Contents Related Reports Idiopathic Membranous Nephropathy Epidemiology Forecast Idiopathic Membranous Nephropathy Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and idiopathic membranous nephropathy epidemiology trends. Nephrotic Syndrome Pipeline Nephrotic Syndrome Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key nephrotic syndrome companies, including GlaxoSmithKline, Goldfinch Bio, Inc., Travere Therapeutics, Inc., Aurinia Pharmaceuticals, Bristol-Myers Squibb, ChemoCentryx, SynAct Pharma AB, among others. Nephrotic Syndrome Market Nephrotic Syndrome Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key nephrotic syndrome companies, including GlaxoSmithKline, Goldfinch Bio, Inc., Travere Therapeutics, Inc., Aurinia Pharmaceuticals, Bristol-Myers Squibb, ChemoCentryx, SynAct Pharma AB, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

2022-11-14

·药明康德

NK细胞组合疗法达100%缓解率、吸入式基因疗法100%完成基因递送… | 一周盘点

▎药明康德内容团队编辑本期看点1. 两项先天细胞接合器（innate cell engager，ICE）疗法AFM13和AFM24的早期临床结果亮眼。2. 通过气溶胶形式给药的基因疗法4D-710具有治疗囊性纤维化的潜力，在100%的检测样本中观察到了广泛的递送和表达。3. 靶向性放射疗法Actimab-A联用化疗治疗复发或难治性急性髓系白血病（AML），使1年及2年生存患者数量翻倍。4. 针对胰腺导管腺癌的溶瘤病毒联合疗法早期结果公布，客观缓解率（ORR）达70%，几乎为历史对照试验中平均ORR（25%）的三倍，临床获益率高达90%。药明康德内容团队整理AFM13与AFM24：公布1/2期临床试验数据Affimed公布了其疗法AFM13与同种异体自然杀伤（NK）细胞疗法联用的1/2期临床试验的积极数据。AFM13是一种先天细胞接合器（ICE），能够同时靶向CD30和CD16A，将先天免疫细胞（和肿瘤细胞“拉到”一起，激活免疫细胞，促进杀死肿瘤。此次公布的数据显示，在以最高剂量水平治疗的24例CD30阳性淋巴瘤患者中，该联合疗法的ORR高达100%，其中完全缓解率（CR）达到了70.8%。安全性方面，患者接受四个周期的治疗时，治疗的耐受性较好。Affimed同时公布了另一款ICE疗法AFM24的两项早期临床试验数据，该疗法靶向EGFR和CD16A。研究结果显示，在接受AFM24单药治疗的难治性EGFR阳性实体瘤患者中，观察到NK细胞的激活及其向肿瘤的迁移。此外，AFM24单药治疗显示出良好的安全性。在接受AFM24联合PD-L1抑制剂atezolizumab治疗的晚期难治性EGFR阳性实体瘤患者中，观察到1例胃癌皮肤转移患者获得了持续的部分缓解（PR），1例胰腺癌患者获得了4+个月的疾病稳定（SD）。在该联合疗法试验中未观察到剂量限制性毒性。4D-710：公布1/2期临床试验的中期数据4D Molecular Therapeutics公布了其基因疗法4D-710治疗肺囊性纤维化的1/2期临床试验的积极中期数据。4D-710是一种由治疗性载体A101和优化的CFTR∆R转基因组成的候选疗法。A101载体能够通过气溶胶形式把疗法递送至整个肺部，在气道细胞中实现高效的基因转导和基因表达，且对人类预先存在的抗体具有抵抗力。此次公布的数据显示，CFTRΔR转基因实现了在来自所有3例患者的100%（11个）的样本中的广泛递送和表达。4D-710的安全性和耐受性得到证实，气雾剂给药后未报道与药物相关的不良事件。Actimab-A：公布1期临床试验数据Actinium Pharmaceuticals公布了其基于锕-225、靶向CD33的靶向性放射疗法Actimab-A与挽救性化疗方案CLAG-M联用治疗复发或难治性AML患者的1期试验积极数据。研究结果显示，所有患者的中位OS为12个月（n=21），1年总生存率为53%，2年总生存率为32%，约为现有治疗方法的两倍。所有剂量队列的ORR为67%，达到细胞遗传学完全缓解（CRc）的患者中，有72%为微小残留病灶（MRD）阴性。在推荐进行2期试验的剂量下，该联合疗法的ORR达到了83%。此外，该联合疗法在TP53突变患者中效果良好，ORR为73%，在先前接受过venetoclax治疗的患者中，ORR为55%。Pelareorep：公布1/2期临床试验的中期数据Oncolytics Biotech公布其开发的溶瘤病毒pelareorep与PD-L1抑制剂和化疗的组合疗法，作为一线治疗晚期/转移性胰腺导管腺癌（PDAC）患者的1/2期临床试验积极中期数据。Pelareorep是一种从常见于环境水域的呼肠孤病毒（reovirus）中分离出来的天然非致病性双链RNA（dsRNA）病毒，有潜力成为治疗实体瘤和血液系统恶性肿瘤的“first-in-class”疗法。研究结果显示，该联合疗法的ORR达70%，几乎为历史对照试验中平均ORR（25%）的三倍。此外，还有2例患者实现了疾病稳定，临床获益率高达90%，表明pelareorep与PD-L1抑制剂和标准化疗有望在晚期/转移性胰腺导管腺癌中发挥协同作用。安全性方面，在该药物组合中未观察到安全信号。SLN360：公布1期临床试验的新数据Silence Therapeutics公布了其靶向脂蛋白（a）——Lp（a）的小干扰RNA（siRNA）疗法SLN360的1期临床试验的新数据。Lp（a）是由肝脏制造的颗粒，由胆固醇、脂肪和蛋白质组成。由于DNA中的特定基因变异，大约五分之一的人具有高水平的Lp（a）。Lp（a）升高的人患早期心脏病、心脏病发作和中风的风险更高。SLN360旨在沉默LPA基因，从而降低Lp（a）水平，有望降低心脏病、心脏病发作和中风的风险。此次公布的数据显示，接受单剂SLN360的健康受试者在5个月内，中位时间平均Lp（a）降低超过80%，一些患者在一年后仍然表现出Lp（a）的大幅降低，约为基线时的50%。此外，随访一年时，任一剂量组均未发现新的药物相关安全性问题。ADI-001：公布1期临床试验数据Adicet Bio公布了其在研同种异体γδCAR-T细胞疗法ADI-001的1期临床数据。ADI-001通过抗CD20的CAR改造的γδT细胞可以靶向恶性B细胞，是一种复发或难治性B细胞非霍奇金淋巴瘤（NHL）的潜在治疗方法。此次公布的数据显示，ADI-001在所有9例患者（包括先前接受过CAR-T细胞疗法治疗的患者）中的ORR和PR均为78%。对于既往接受过靶向CD19的自体CAR-T细胞治疗的4例患者，ORR和CR率均为100%。该研究中，ADI-001表现出持续良好的安全性和耐受性，未报告移植物抗宿主病或剂量限制性毒性事件。2022年4月，ADI-001被美国FDA授予快速通道资格，用于治疗复发或难治性B细胞NHL。ADP-A2M4CD8：公布1期临床试验数据Adaptimmune Therapeutics公司发布了旗下靶向MAGE-A4的T细胞疗法的最新临床1期数据。ADP-A2M4CD8可以特异性地靶向MAGE-A4，这是一种在多种实体瘤中表达的癌症抗原。这种疗法的独到之处在于，T细胞在表达针对MAGE-A4的T细胞受体的同时，也表达了CD8α共受体。临床前研究结果表明，CD8α的共表达可以增强针对实体瘤的免疫反应，并通过将CD4+细胞转化为CD8+的杀伤性T细胞或细胞毒性T细胞、同时保留CD4+细胞的辅助性免疫功能来增强抗肿瘤活性。本次所发布的数据显示，经过单剂ADP-A2M4CD8治疗后，晚期卵巢癌、尿路上皮癌和头颈癌患者中的ORR为52%，这些患者先前接受过抗癌治疗。整个试验的ORR为37%，其中卵巢癌的ORR为43%，尿路上皮癌的ORR为57%。该试验中，治疗的持久性持续增加，目前中位缓解时间已达到约20周。最近，该疗法还获得了美国FDA授予的再生医学高级疗法认定（RMAT），用于治疗铂耐药卵巢癌。INB-1001：公布1期临床试验数据IN8bio公布了其同种异体γ-δT细胞疗法INB-100在接受异体造血干细胞移植（HSCT）的高危AML患者中的1期试验的积极数据。数据显示，INB-100在这类患者中具有诱导长期持久反应的潜力。接受治疗的3例患者均保持CR，响应持续时间均超过12个月，其中两例响应已超过24个月，目前仍在随访中。截至目前，INB-100展示出可控的安全性，没有剂量限制性毒性。AlloStem：IND申请获得FDA许可AlloStem是一种用于治疗1型糖尿病的新型同种异体细胞疗法。利用围产期组织衍生细胞（PRDC）的力量，AlloStem可以实现多种潜能，包括自我更新能力、低抗原性、减低毒性和大规模临床扩增。GNOS-PV02：公布1b/2a期临床试验数据Geneos Therapeutics公布了其个体化治疗性癌症疫苗（PTCV）GNOS-PV02与质粒编码的IL-12以及PD-1抑制剂pembrolizumab联用治疗无法切除或转移性肝细胞癌（HCC）的早期临床试验数据。GNOS-PV02是一款基于DNA质粒递送的新抗原疫苗。通过对每例患者的肿瘤进行测序，发现基于每个患者独特的肿瘤突变产生的新抗原，然后将表达这些新抗原的DNA序列导入到DNA质粒中。研究结果显示，23例可评估患者的ORR为30.4%。所有24例患者的疾病稳定率（DCR）为54.2%，包括2例CR，5例PR，10例SD，还有一例患者被判定为放射学PR。此外，与疫苗接种相关的不良事件仅限于1级和2级VTP-300：公布1b/2a期临床试验数据Vaccitech Limited公布了其开发的VTP-300单药或与单次给药的低剂量PD-1抑制剂nivolumab联用治疗慢性乙型肝炎的早期临床试验数据。VTP-300是一种与疫苗作用机制非常类似的免疫疗法。利用Vaccitech的黑猩猩腺病毒载体（ChAdOx1）和改良牛痘安卡拉病毒（MVA）载体表达乙肝病毒抗原，激发抗HBV的免疫应答，有望为慢性乙肝患者带来功能性治愈。此次公布的数据显示，VTP-300能够诱导慢性乙型肝炎患者的乙型肝炎表面抗原持续减少，并观察到针对所有编码抗原的强烈T细胞反应。在该试验中，尚未发现与治疗相关的严重不良事件，一过性的转氨酶升高也较为罕见。ALPN-303：公布1期临床试验数据Alpine Immune Sciences公布了其细胞因子拮抗剂ALPN-303在健康受试者中的1期试验的结果。ALPN-303是在B细胞的活化和存活中起关键作用的BAFF（B细胞活化因子）和APRIL（一种增殖诱导配体）细胞因子的双重拮抗剂。ALPN-303正在被开发用于多种B细胞和/或自身抗体相关疾病，如系统性红斑狼疮、肾小球肾炎和自身免疫性血细胞减少症。该临床试验中，ALPN-30具有良好的耐受性，并表现出与剂量相关的药代动力学和靶向药效学作用，并能够剂量依赖性地降低与IgA肾病的发病机制有关的关键分子——血清半乳糖缺陷的IgA1（Gd-IgA1）。FS118：公布1期临床试验数据F-star Therapeutics公布了其双特异性抗体FS118治疗PD-L1获得性耐药肿瘤患者的1期临床试验数据。FS118在抗体的可变区携带两个靶向PD-L1的蛋白域，并且在抗体的Fc端添加了两个靶向LAG-3的蛋白域，形成一款同时靶向LAG-3和PD-L1四价双特异性IgG1抗体。研究结果显示，PD-L1获得性耐药患者中显示出持续的、可溶性LAG-3水平增加（即LAG-3脱落）和外周效应细胞增加。在接受剂量>1 mg/kg的FS118时，DCR为54.8%，1例甲状腺未分化癌患者实现了PR。FS118在所有剂量水平上均具有良好的耐受性，未发现治疗相关的严重不良事件。ONC-392：公布1/2期临床试验数据OncoC4公布了其抗CTLA-4单克隆抗体ONC-392联用PD-1抑制剂pembrolizumab治疗晚期实体肿瘤患者的1/2期临床试验的积极数据。在转移性癌症患者研究的剂量递增部分中，可评估患者的ORR为30%，DCR为90%。剂量扩展的初步结果显示，6例可评估的转移性黑色素瘤患者中有5例实现了PR，1例实现了SD。VB119：公布1b/2a期临床试验的初步数据ValenzaBio公布了其单克隆抗体VB119的1a/2b期临床试验的初步积极结果。VB119具有增强的抗体依赖性细胞毒性，并能与CD19有效结合，被开发用于治疗原发性膜性肾病（PMN）。PMN是一种自身免疫性肾小球疾病，通常表现为蛋白尿，并可能导致肾功能受损。约70%的PMN病例是由针对成熟B细胞（如浆母细胞和浆细胞）分泌的磷脂酶A2受体（PLA2R）的自身抗体引起的。VB119旨在通过消耗表达CD19的B细胞来减少致病性自身抗体的产生，有可能为PMN患者提供疾病修饰治疗。该试验结果显示，VB119可以使B细胞和抗PLA2R自身抗体显著减少。4例可评估的患者中有3例在开始治疗后不到一个月的时间内实现了蛋白尿的迅速减少。在≥40周的随访中，1例患者实现了蛋白尿的完全缓解。截至目前，VB119的耐受性良好。BION-1301：公布1/2期临床试验数据Chinook Therapeutics公布了其新型抗APRIL单克隆抗体BION-1301治疗IgA肾病患者的1/2期临床试验的中期更新结果。阻断APRIL是一种通过降低半乳糖缺陷IgA1（Gd-IgA1）的循环水平来治疗IgA肾病的潜在疾病改善方法。此次公布的数据显示，BION-1301能够持续降低IgA肾病患者的IgA和Gd-IgA1的水平，并具有良好的耐受性。治疗100周时，队列1中的2例患者的平均尿蛋白下降了71%。Efzofitimod：公布1b/2a期临床试验数据aTyr Pharma公布了其潜在“first-in-class”的免疫调节剂efzofitimod用于治疗肺结节病的1b/2a期随机、双盲、安慰剂对照临床试验的阳性结果。Efzofitimod是一种融合蛋白，由人源抗体的FC段与组氨酰-tRNA合成酶的免疫调节结构域融合而成，是神经纤维蛋-2（NRP2）的选择性调节剂，可在炎症性疾病状态下下调先天性和适应性免疫反应。该研究表明，efzofitimod在所有剂量下都是安全且耐受性良好的。与安慰剂相比，efzofitimod能够减少类固醇的使用，同时在肺功能、肺结节病关键生理指标和患者的生活质量方面显示出改善。OCE-205：公布1期临床试验数据Ocelot Bio公布了OCE-205的1期临床试验的结果。OCE-205是一种对加压素（V1a）受体具有选择性的混合激动剂-拮抗剂治疗肽，有望改善终末期肝病（ESLD）并发症患者的预后。由于其混合的V1a激动剂/拮抗剂活性，OCE-205治疗被设计用于缓解门脉高压，同时提供具有上限的疗效，避免了完全激动剂引起的过度血管收缩导致的缺血性损伤和潜在的其他严重不良事件，如呼吸衰竭。此次公布的数据显示，在健康受试者中，OCE-205给药导致平均动脉压升高，具有良好的安全性。NT-I7：公布1b期临床试验的初步数据NeoImmuneTech公布了其NT-I7（efineptakin alfa）与靶向CD19的CAR-T细胞疗法tisagenlecleucel联合治疗复发/难治性大B细胞淋巴瘤（r/r LBCL）的1b期临床试验的数据。Tisagenlecleucel是r/r LBCL患者的标准治疗。NT-I7是一种将两个IL-7蛋白域和长效hyFc蛋白域融合在一起的临床阶段的长效人IL-7。此次公布的结果显示，NT-I7能够使绝对淋巴细胞计数持续增加，外周血中CAR-T细胞的绝对数量增加。这种组合有望增加CAR-T细胞的增殖和持久性，提高肿瘤响应率并改善临床结果。PCLX-001：IND申请获得FDA许可PCLX-001是一种潜在“first-in-class”的小分子N-肉豆蔻酰转移酶（NMT）抑制剂，最初被设想用于治疗白血病和淋巴瘤。肉豆蔻酰化是癌细胞增殖和存活的基础，PCLX-001可抑制癌细胞中的这一过程发挥抗肿瘤作用。在临床前的动物模型中，PCLX-001被证明可以抑制肺癌和乳腺癌的生长。此前，PCLX-001已获得了FDA授予的孤儿药资格。AT-752：公布1期临床试验数据Atea Pharmaceuticals公布了来源于其嘌呤核苷酸前药平台的口服抗病毒药物AT-752的1期临床试验数据。该药通过减弱登革热病毒聚合酶的作用起效，能够抑制病毒的复制。在临床前研究中，AT-752显示出对所有登革热血清型具有体内及体外的抗病毒活性。1期试验显示，即使在试验设计的最高剂量下，AT-752依然耐受性良好，并迅速达到高于体外EC90的血浆水平。药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息‍▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明‍直播间”，观看相关话题的直播讨论与精彩回放‍‍参考资料（可上下滑动查看）[1] Atea Pharmaceuticals Presents Favorable AT-752 Phase 1 Data for Treatment of Dengue Fever at American Society of Tropical Medicine & Hygiene 2022 Annual Meeting. Retrieved November 3, 2022, from https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-presents-favorable-752-phase-1-data[2] Creative Medical Technology Holdings Announces FDA Clearance of Investigational New Drug (IND) Application for AlloStem™, a Novel Cell Therapy for the Treatment of Type 1 Diabetes. Retrieved November 3, 2022, from https://creativemedicaltechnology.investorroom.com/2022-11-03-Creative-Medical-Technology-Holdings-Announces-FDA-Clearance-of-Investigational-New-Drug-IND-Application-for-AlloStem-TM-,-a-Novel-Cell-Therapy-for-the-Treatment-of-Type-1-Diabetes[3] AFFIMED ANNOUNCES PRESENTATION OF PHASE 1/2 DATA FROM AFM13 IN COMBINATION WITH ALLOGENEIC NK CELLS AND PRECLINICAL AFM28 DATA AT ASH 2022 ANNUAL MEETING. Retrieved November 3, 2022, from https://www.affimed.com/affimed-announces-presentation-of-phase-1-2-data-from-afm13-in-combination-with-allogeneic-nk-cells-and-preclinical-afm28-data-at-ash-2022-annual-meeting/[4] AFFIMED PROVIDES DATA UPDATE FROM TWO PHASE 1/2A TRIALS WITH ITS INNATE CELL ENGAGER AFM24 IN SOLID TUMOR PATIENTS AT THE 37TH SITC ANNUAL MEETING. Retrieved November 7, 2022, from https://www.affimed.com/affimed-provides-data-update-from-two-phase-1-2a-trials-with-its-innate-cell-engager-afm24-in-solid-tumor-patients-at-the-37th-sitc-annual-meeting/[5] Adicet Bio Reports ASH Abstract Data from Ongoing ADI-001 Phase 1 Trial in Relapsed or Refractory Aggressive B-Cell Non-Hodgkin’s Lymphoma (NHL). Retrieved November 3, 2022, from https://investor.adicetbio.com/news-releases/news-release-details/adicet-bio-reports-ash-abstract-data-ongoing-adi-001-phase-1[6] Alpine Immune Sciences Presents Update Of ALPN-303 Phase 1 (RUBY-1) Clinical Data at the American Society of Nephrology Kidney Week 2022 Meeting. Retrieved November 3, 2022, from https://ir.alpineimmunesciences.com/news-releases/news-release-details/alpine-immune-sciences-presents-update-alpn-303-phase-1-ruby-1[7] Pacylex Announces FDA Clearance of IND Application for PCLX-001 to Treat Acute Myeloid Leukemia. Retrieved November 3, 2022, from https://www.pacylex.com/post/fda-clearance-aml[8] VALENZABIO ANNOUNCES POSITIVE PRELIMINARY DATA FROM PHASE 1B/2A TRIAL OF VB119, AN ANTI-CD19 MONOCLONAL ANTIBODY FOR THE TREATMENT OF PRIMARY MEMBRANOUS NEPHROPATHY. Retrieved November 3, 2022, from https://www.valenzabiotech.com/news/valenzabio-announces-positive-preliminary-data-from-phase-1b-2a-trial-of-vb119-an-anti-cd19-monoclonal-antibody-for-the-treatment-of-primary-membranous-nephropathy/#release[9] 4D Molecular Therapeutics Announces Interim Clinical Data from Phase 1/2 Clinical Trial of 4D-710 for Cystic Fibrosis Lung Disease at NACFC 2022. Retrieved November 3, 2022, from https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4d-molecular-therapeutics-announces-interim-clinical-data-phase[10] Actinium Announces Positive 1-Year and 2-Year Overall Survival Data for Patients with Relapsed or Refractory AML in Phase 1 Actimab-A CLAG-M Combination Trial. Retrieved November 3, 2022, from https://ir.actiniumpharma.com/press-releases/detail/430/actinium-announces-positive-1-year-and-2-year-overall[11] IN8bio to Present Positive Early Data from Ongoing Phase 1 Study of INB-100 at the 64th American Society of Hematology Annual Meeting. Retrieved November 3, 2022, from https://investors.in8bio.com/news-releases/news-release-details/in8bio-present-positive-early-data-ongoing-phase-1-study-inb-100[12] Silence Therapeutics Presents New Analysis from SLN360 Phase 1 Single Dose Study in High Lipoprotein(a) at the American Heart Association (AHA) 2022 Annual Meeting. Retrieved November 5, 2022, from https://www.businesswire.com/news/home/20221105005027/en[13] Ocelot Bio Presents Phase 1 Data Highlighting Activity and Safety of OCE-205 atAASLD The Liver Meeting. Retrieved November 4, 2022, from https://www.ocelotbio.com/news-4th-november[14] NeoImmuneTech to Present First Data on NT-I7 (efineptakin alfa) in Combination with CAR-T tisagenlecleucel, at 2022 ASH Annual Meeting. Retrieved November 4, 2022, from https://www.prnewswire.com/news-releases/neoimmunetech-to-present-first-data-on-nt-i7-efineptakin-alfa-in-combination-with-car-t-tisagenlecleucel-at-2022-ash-annual-meeting-301668788.html[15] CHINOOK THERAPEUTICS PRESENTS UPDATED DATA FROM BION-1301 PHASE 1/2 TRIAL IN PATIENTS WITH IGA NEPHROPATHY (IGAN) AND CHK-336 PRECLINICAL EFFICACY DATA AT THE AMERICAN SOCIETY OF NEPHROLOGY (ASN) KIDNEY WEEK 2022. Retrieved November 4, 2022, from https://investors.chinooktx.com/news-releases/news-release-details/chinook-therapeutics-presents-updated-data-bion-1301-phase-12-0[16] ONCOC4 TO PRESENT POSITIVE DATA FROM ONGOING PHASE 1/2 PRESERVE-001 TRIAL OF ONC-392 IN COMBINATION WITH PEMBROLIZUMAB AT SITC 2022. Retrieved November 7, 2022, from https://www.oncoc4.com/index.php/blog/news-releases/item/12-oncoc4-to-present-positive-data-from-ongoing-phase-1-2-preserve-001-trial-of-onc-392-in-combination-with-pembrolizumab-at-sitc-2022[17] Geneos Therapeutics Announces Positive Clinical Data for Personalized Therapeutic Cancer Vaccines in Ongoing Liver Cancer Trial. Retrieved November 7, 2022, from https://www.geneostx.com/geneos-therapeutics-announces-positive-clinical-data-for-personalized-therapeutic-cancer-vaccines-in-ongoing-liver-cancer-trial/[18] F-star Therapeutics Announces Publication of Phase 1 Dose-Escalation Trial of FS118 in Patients with Advanced Cancer and PD-L1 Resistance in Clinical Cancer Research. Retrieved November 7, 2022, from https://investors.f-star.com/news-releases/news-release-details/f-star-therapeutics-announces-publication-phase-1-dose[19] Vaccitech Provides Update on Ongoing VTP-300 Phase 1b/2a Trial Showing Sustained Reductions of HBsAg in Patients with Chronic Hepatitis B. Retrieved November 7, 2022, from https://investors.vaccitech.co.uk/news-and-events/news-releases/news-release-details/vaccitech-provides-update-ongoing-vtp-300-phase[20] Adaptimmune Reports Increased Response Rate and Durability of Response in Its Phase 1 SURPASS trial; ORR Now 52% Across Ovarian, Urothelial, and Head & Neck Cancers，Retrieved November 8, 2022, from https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/234/adaptimmune-reports-increased-response-rate-and-durability[21] aTyr Pharma Announces Publication of Positive Data from Phase 1b/2a Clinical Study of Efzofitimod for the Treatment of Pulmonary Sarcoidosis in the Journal CHEST. Retrieved November 9, 2022, from https://investors.atyrpharma.com/news-releases/news-release-details/atyr-pharma-announces-publication-positive-data-phase-1b2a免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果放射疗法基因疗法细胞疗法临床1期

2022-11-03

·BioSpace

ValenzaBio Announces Positive Preliminary Data from Phase 1b/2a Trial of VB119, an Anti-CD19 Monoclonal Antibody for the Treatment of Primary Membranous Nephropathy

- VB119 resulted in profound reductions in B-cells and anti-PLA2R autoantibodies - Three of four evaluable patients had rapid reduction in proteinuria less than one month after initiation of therapy - Complete remission of proteinuria was achieved for the single patient with ≥40 weeks follow up - VB119 was well-tolerated; no study drug related SAEs were reported BETHESDA, Md.--(BUSINESS WIRE)-- ValenzaBio, Inc., a biopharmaceutical company developing monoclonal antibody (mAb) therapeutics for autoimmune and inflammatory indications, today announced positive initial results from its open label Phase 1a/2b clinical trial of VB119, a B-cell depleting mAb with enhanced antibody-dependent cellular cytotoxicity and potent binding to CD19, for the treatment of primary membranous nephropathy (PMN). These data represent the first clinical proof-of-concept for an anti-CD19 antibody in this disease and demonstrate potential differentiation from other therapies used in this indication. The data will be presented today during a poster session titled, "Glomerular Diseases: Podocytopathies and Nephrotic Syndromes" at the 2022 American Society of Nephrology (ASN) Annual Meeting from 10:00 AM to 12:00 PM ET (Abstract #TH-PO456). The poster can be found on the ValenzaBio website at the following address: . Primary Membranous Nephropathy (PMN) PMN, also known as idiopathic membranous nephropathy, is an autoimmune glomerular disease and is one of the leading causes of non-diabetic nephrotic syndrome. PMN causes the body to lose considerable amounts of protein in the urine (called proteinuria) and can lead to impaired kidney function over time. Approximately 70% of cases of PMN are caused by autoantibodies directed against the phospholipase A2 receptor (PLA2R) that are secreted from mature B-cells, such as plasmablasts and plasma cells. VB119 aims to reduce the production of pathogenic autoantibodies via the depletion of CD19-expressing B-cells with the potential to provide a disease modifying treatment for patients with PMN. Initial proof-of-concept results from Phase 1b The Phase 1b/2a trial is an open-label, sequential-cohort, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VB119 in patients with PMN. Findings presented today are from an initial five participants enrolled in the trial as of October 3, 2022, across two dose cohorts in which patients received either 100 mg or 200 mg doses of VB119. Four patients administered at least two doses of VB119 have available follow up data out to at least Week 4. Of those patients, three have received the 100 mg dose and one patient has received the 200 mg dose. The three patients at the 100 mg dose level achieved complete (<5 cells/µL) and durable B-cell depletion by Week 12, and experienced substantial reductions in proteinuria, ranging from 34% to 95%. One patient in the 100 mg dose cohort achieved a complete remission of proteinuria, from a baseline proteinuria of 4.10 g/g to 0.20 g/g at Week 40. Two patients in the 100 mg dose cohort were anti-PLA2R antibody positive at baseline, and both achieved >50% reduction in serum anti-PLA2R autoantibodies from baseline to levels <20 RU/mL. The single patient enrolled in the 200 mg dose cohort achieved complete depletion of B-cells by Week 4. VB119 has been well-tolerated to date; one patient experienced an SAE that was deemed unrelated to study drug. “PMN is a debilitating glomerular disease with limited treatment options, none of which produce high rates of complete remission,” said Dr. Greg Keenan, M.D., chief medical officer of ValenzaBio. “We believe these data demonstrate that CD19-directed B-cell depletion is capable of targeting pathogenic cell types in this disease, namely plasmablasts and plasma cells, which can potentially result in more rapid responses and higher rates of complete remission.” “Available treatment regimens fail to achieve complete remission in most patients with primary membranous nephropathy. More effective therapies with limited toxicity are needed to improve outcomes in this population,” noted Frank B. Cortazar, M.D., Director of the New York Nephrology Vasculitis and Glomerular Center, and a principal investigator for the VB119 trial. “The preliminary VB119 data are encouraging, with rapid declines in PLA2R antibody levels and improvements in proteinuria, providing an early signal for efficacy in a disease process that remains a therapeutic challenge for clinicians and patients.” About ValenzaBio, Inc. ValenzaBio is a privately held biopharmaceutical company developing safe and effective therapies for autoimmune and inflammatory diseases. The company is advancing a pipeline of differentiated monoclonal antibodies with best-in-class properties, targeting clinically validated mechanisms of action, to provide improved treatment options for patients. For more information, please visit .

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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


NCT04652570 (ASN2022) 人工标引	临床1/2期	特发性膜性肾病	3	VB119	構網願蓋選製齋淵襯鏇(積遞築壓襯鑰繭獵鹽夢) = There were no treament related adverse events. 餘糧網繭鏇夢鏇齋餘齋 (淵觸鹽蓋鬱鑰夢遞鹽齋 )	积极	2022-11-03
VB119 (ASN2022)	临床1/2期	特发性膜性肾病 phospholipase A2 receptor (PLA2R)	30	VB119	遞壓窪顧範構醖顧蓋積(鏇襯範鹽獵壓製蓋選鹽) = 製蓋艱選鬱鹽淵齋艱壓鏇齋齋遞選選積鹽壓鹽 (鑰壓願膚衊膚夢觸艱醖 )	积极	2022-11-03