作者: Esmaeili, Seyed-Alireza ; Kamal Kheder, Ramiar ; Momtazi, Amir Abbas ; Modarres Moghadam, Reyhane ; Najmaldin, Soran K ; Rezaieyazdi, Zahra ; Mollazadeh, Samaneh ; Tabasi, Nafiseh ; Mansouri, Atena ; Mahmoudi, Mahmoud ; Shapouri-Moghaddam, Abbas ; Nikpoor, Amin Reza

Background::Systemic lupus erythematosus (SLE) is a complex autoimmune disease recognized by elevated activity of autoimmune cells, loss of tolerance, and decreased regulatory T cells producing inhibitory cytokines. Despite many efforts, the definitive treatment for lupus has not been fully understood. Curcumin (CUR) and berberine (BBR) have significant immunomodulatory roles and anti-inflammatory properties that have been demonstrated in various studies. This study aimed to investigate the anti-inflammatory properties of CUR and BBR on human monocyte-derived dendritic cells (DCs) with an special focus on the maturation and activation of DCs.Methods::Human monocytes were isolated from the heparinized blood of SLE patients and healthy individuals, which were then exposed to cytokines (IL-4 and GM-CSF) for five days to produce immature DCs. Then, the obtained DCs were characterized by FITC-uptake assay and then cultured in the presence of CUR, BBR, or lipopolysaccharide (LPS) for 48 h. Finally, the maturation of DCs was analyzed by the level of maturation using flow cytometry or real-time PCR methods.Results::The results showed promising anti-inflammatory effects of CUR and BBR in comparison with LPS, supported by a significant reduction of not only co-stimulatory and antigen-presenting factors such as CD80, CD86, CD83, CD1a, CD14, and HLA-DR but also inflammatory cytokines such as IL-12.Conclusion::CUR and BBR could arrest DC maturation and develop a tolerogenic DC phenotype that subsequently promoted the expression of inhibitory cytokines and reduced the secretion of proinflammatory markers.

2024-02-01·Dermatitis®

A Review of Dupilumab-Induced Adverse Events to Dermatologists and the Potential Pathogenesis in the Treatment of Atopic Dermatitis

Review

作者: Tsai, Jun-Hong ; Tsai, Tsen-Fang

Dupilumab, a monoclonal antibody targeting interleukin-4 antibody, is approved for use in many type 2 inflammatory diseases, including atopic dermatitis. It is generally well tolerated with no need of routine laboratory monitoring. However, several adverse events have been reported during real-world practice and in pivotal trials. We conducted a systematic literature research of the PubMed, Medline, and Embase databases to identify articles recording the clinical manifestation and potential pathogenesis of these adverse events with interests (AEIs) to dermatologists. In total, 547 cases from 134 studies have developed 39 AEIs 1 day to 2.5 years after dupilumab treatment. The most common AEIs are facial and neck dermatitis (299 cases), psoriasis (70 cases), arthralgia (56 cases), alopecia (21 cases), cutaneous T cell lymphoma (19 cases), severe ocular diseases (19 cases), and drug eruption (6 cases). Most of the AEIs recorded in this review resolved or improved after dupilumab discontinuation or the addition of another treatment, whereas 3 of the cases died of severe AEI. The potential pathogenesis included T help type 1 (Th1)/T help type 2 (Th2) imbalance, Th2/T help type 17 (Th17) imbalance, immune reconstitution, hypersensitivity reaction, transient hypereosinophilia related, and Th1 suppression. Clinicians should be alert of these AEIs for timely diagnosis and appropriate treatment.

2024-02-01·Proteins: Structure, Function, and Bioinformatics

Lessons on protein structure from interleukin‐4: All disulfides are not created equal

Article

作者: Rodrigues, J Rui ; Müller, Thomas D ; Vaz, Daniela C ; Brito, Rui M M ; Loureiro-Ferreira, Nuno ; Redfield, Christina ; Sebald, Walter

AbstractInterleukin‐4 (IL‐4) is a hematopoietic cytokine composed by a four‐helix bundle stabilized by an antiparallel beta‐sheet and three disulfide bonds: Cys3‐Cys127, Cys24‐Cys65, and Cys46‐Cys99. IL‐4 is involved in several immune responses associated to infection, allergy, autoimmunity, and cancer. Besides its physiological relevance, IL‐4 is often used as a “model” for protein design and engineering. Hence, to understand the role of each disulfide in the structure and dynamics of IL‐4, we carried out several spectroscopic analyses (circular dichroism [CD], fluorescence, nuclear magnetic resonance [NMR]), and molecular dynamics (MD) simulations on wild‐type IL‐4 and four IL‐4 disulfide mutants. All disulfide mutants showed loss of structure, altered interhelical angles, and looser core packings, showing that all disulfides are relevant for maintaining the overall fold and stability of the four‐helix bundle motif, even at very low pH. In the absence of the disulfide connecting both protein termini Cys3‐Cys127, C3T‐IL4 showed a less packed protein core, loss of secondary structure (~9%) and fast motions on the sub‐nanosecond time scale (lower S2 order parameters and larger τc correlation time), especially at the two protein termini, loops, beginning of helix A and end of helix D. In the absence of Cys24‐Cys65, C24T‐IL4 presented shorter alpha‐helices (14% loss in helical content), altered interhelical angles, less propensity to form the small anti‐parallel beta‐sheet and increased dynamics. Simultaneously deprived of two disulfides (Cys3‐Cys127 and Cys24‐Cys65), IL‐4 formed a partially folded “molten globule” with high 8‐anilino‐1‐naphtalenesulphonic acid‐binding affinity and considerable loss of secondary structure (~50%decrease), as shown by the far UV‐CD, NMR, and MD data.

项与 Binetrakin 相关的新闻（医药）

2024-03-01

·信达生物

信达生物IBI3002（抗IL-4Rα/TSLP双特异性抗体）临床I期研究在澳大利亚完成首例受试者给药

2024年3月1日，美国罗克维尔和中国苏州——信达生物制药集团（香港联交所股票代码：01801），一家致力于研发、生产和销售肿瘤、自身免疫、代谢及心血管、眼科等重大疾病领域创新药物的生物制药公司，宣布IBI3002的首次人体（FIH）临床I期研究已在澳大利亚完成首例受试者给药。IBI3002是一种全球首创（first-in-class）的靶向白细胞介素4受体α（IL-4Rα）和胸腺基质淋巴细胞生成素（TSLP）的双特异性抗体。本项FIH研究（NCT06213844）是一项随机、双盲、安慰剂对照、单次给药剂量递增（SAD）研究，旨在评估IBI3002在健康受试者和轻中度哮喘受试者中的安全性、耐受性、药代动力学（PK）和药效学（PD，仅在哮喘受试者中），以支持IBI3002后续全球临床开发。IBI3002是信达生物自主研发的人源化双特异性抗体，靶向细胞表面IL-4Rα和警报素细胞因子TSLP，用于治疗包括哮喘在内的炎症性疾病。IL-4受体介导了IL-4信号通路（1型和2型）和IL-13信号通路（2型），两种细胞因子信号通路在2型炎症性疾病的病理生理学中均起关键作用1。TSLP是一种上皮细胞来源的警报素细胞因子，可触发哮喘中的2型和非2型炎症2。IBI3002具有高效的IL-4Rα和TSLP共同阻断功能。体外功能学实验显示比同靶点的已上市单克隆抗体更优。通过同时靶向IL-4Rα和TSLP，IBI3002具有抑制2型和非2型炎症的潜力，在抑制2型炎症方面具有潜在的协同作用，有望在治疗2型炎症性疾病中展现优效性。信达生物制药集团临床开发副总裁钱镭博士表示：“在过去的几十年里，医疗界对哮喘的病理生理机制/表型和治疗选择的认知有了显著增加，特别是通过引入生物制剂治疗重度哮喘这一精准治疗的策略，为哮喘管理带来革命性的变革。高选择性药物通过靶向免疫炎症级联的特定步骤，有潜力进一步突破广大严重哮喘患者的治疗局限，并有望在多种重度哮喘炎症表型中实现最佳疾病控制；同时，我们也期待推进该分子未来在哮喘和其他多种炎症性疾病中的进一步开发。”关于哮喘- 滑动查看更多介绍 -哮喘是一种由多种免疫细胞、细胞因子及炎症介质介导，累及全年龄段人群的异质性疾病，以喘息、气促、咳嗽和胸闷等多种症状为特征，与慢性气道炎症、可变的气流受限和气道高反应性相关3。根据2015年全球疾病负担（GBD）研究，约有3.58亿人患有哮喘4。根据气道或外周血细胞特征，哮喘可大致分为嗜酸性粒细胞性和非嗜酸性粒细胞性哮喘。嗜酸性粒细胞炎症主要由2型炎症驱动，包括2型辅助T细胞和2型固有淋巴细胞5。与嗜酸性粒细胞性哮喘相比，对于非嗜酸性粒细胞性哮喘的了解仍不充分6。高达10%的成人哮喘患者和2.5%的儿童哮喘患者患有重度哮喘7。尽管接受了足够的大剂量吸入治疗，重度哮喘患者仍存在症状持续或频繁急性加重，需要反复系统性糖皮质激素短期或维持治疗8。在这些患者中，需要给予额外治疗（可能包括生物制剂）以减轻疾病负担2,3。关于IBI3002- 滑动查看更多介绍 -IBI3002是一款全球首创靶向细胞表面IL-4Rα和警报素细胞因子TSLP的双特异性抗体。该分子具有高效的IL-4Rα和TSLP共同阻断功能。体外功能学实验显示比同靶点的已上市单克隆抗体更优。通过同时靶向IL-4Rα和TSLP，IBI3002具有治疗包括哮喘在内多种炎症性疾病的潜力。IL-4是2型淋巴细胞分化的中心介质；它诱导产生2型相关细胞因子，如IL-5、IL-9、IL-13和/或2型相关趋化因子，如胸腺和活化调节趋化因子(TARC/CCL17)和嗜酸性粒细胞趋化因子-3。IL-4参与调节B细胞的同种型类别转换以产生血清IgE，并通过释放IL-5招募嗜酸性粒细胞。尽管IL-13在这些促炎过程中显示出一些冗余性，但它在介导杯状细胞增生、粘液产生、平滑肌收缩性和气道高反应性方面具有额外的作用。总的来说，IL-4和IL-13共同在2型炎症中起关键作用1。TSLP是一种上皮细胞来源的警报素细胞因子，它在2型炎症诱导和通过IL-4、IL-5和IL-13产生的Th2细胞分化与成熟中占据上游位置。TSLP也被认为是哮喘中非2型炎症的触发因素2。关于信达生物- 滑动查看更多介绍 -“始于信，达于行”，开发出老百姓用得起的高质量生物药，是信达生物的使命和目标。信达生物成立于2011年，致力于开发、生产和销售肿瘤、代谢及心血管、自身免疫、眼科等重大疾病领域的创新药物。公司已有10款产品获得批准上市，同时还有3个品种在NMPA审评中，4个新药分子进入III期或关键性临床研究，另外还有19个新药品种已进入临床研究。公司与海内外药企深入合作加速药物创新，与礼来、罗氏、赛诺菲、Adimab、Incyte和MD Anderson 癌症中心等国际合作方达成30多项战略合作。信达生物在不断开发创新药物、谋求自身发展的同时，始终心怀科学善念，坚守“以患者为中心”，心系患者并关注患者家庭，积极履行社会责任。信达生物希望和大家一起努力，提高中国生物制药产业的发展水平，以满足百姓用药可及性和人民对生命健康美好愿望的追求。详情请访问公司网站：www.innoventbio.com或公司领英账号：Innovent Biologics。声明：信达不推荐任何未获批的药品/适应症使用。参考文献：1.Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production[J]. Cytokine, 2015, 75(1): 14-24.2. Brusselle G G, Koppelman G H. Biologic therapies for severe asthma[J]. New England Journal of Medicine, 2022, 386(2): 157-171.3. Global Initiative for Asthma. 2023 GINA Report, Global Strategy for Asthma Management and Prevention. 2023.4. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet Respir Med. 2017 Oct;5(10 ):e30]. Lancet Respir Med. 2017;5(9):691-706.5. Gans MD, Gavrilova T. Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes. Paediatr Respir Rev. 2020;36:118-127.6. Israel E, Reddel H K. Severe and difficult-to-treat asthma in adults[J]. New England Journal of Medicine, 2017, 377(10): 965-976.7. Settipane RA, Kreindler JL, Chung Y, Tkacz J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol 2019; 123(6): 564-572.e3.8.Caminati M, Vaia R, Furci F, Guarnieri G, Senna G. Uncontrolled Asthma: Unmet Needs in the Management of Patients. J Asthma Allergy. 2021;14:457-466.前瞻性声明本新闻稿所发布的信息中可能会包含某些前瞻性表述。这些表述本质上具有相当风险和不确定性。在使用“预期”、“相信”、“预测”、“期望”、“打算”及其他类似词语进行表述时，凡与本公司有关的，目的均是要指明其属前瞻性表述。本公司并无义务不断地更新这些预测性陈述。这些前瞻性表述乃基于本公司管理层在做出表述时对未来事务的现有看法、假设、期望、估计、预测和理解。这些表述并非对未来发展的保证，会受到风险、不确性及其他因素的影响，有些乃超出本公司的控制范围，难以预计。因此，受我们的业务、竞争环境、政治、经济、法律和社会情况的未来变化及发展的影响，实际结果可能会与前瞻性表述所含资料有较大差别。

临床1期

2024-03-01

·美通社

信达生物宣布IBI3002（抗IL-4Rα/TSLP双特异性抗体）临床I期研究在澳大利亚完成首例受试者给药

美国罗克维尔和中国苏州 2024年3月1日 /美通社/ -- 信达生物制药集团（香港联交所股票代码：01801），一家致力于研发、生产和销售肿瘤、自身免疫、代谢及心血管、眼科等重大疾病领域创新药物的生物制药公司，宣布IBI3002的首次人体（FIH）临床I期研究已在澳大利亚完成首例受试者给药。IBI3002是一种全球首创（first-in-class）的靶向白细胞介素4受体α（IL-4Rα）和胸腺基质淋巴细胞生成素（TSLP）的双特异性抗体。本项FIH研究（NCT06213844）是一项随机、双盲、安慰剂对照、单次给药剂量递增（SAD）研究，旨在评估IBI3002在健康受试者和轻中度哮喘受试者中的安全性、耐受性、药代动力学（PK）和药效学（PD，仅在哮喘受试者中），以支持IBI3002后续全球临床开发。 IBI3002是信达生物自主研发的人源化双特异性抗体，靶向细胞表面IL-4Rα和警报素细胞因子TSLP，用于治疗包括哮喘在内的炎症性疾病。IL-4受体介导了IL-4信号通路（1型和2型）和IL-13信号通路（2型），两种细胞因子信号通路在2型炎症性疾病的病理生理学中均起关键作用 1 。TSLP是一种上皮细胞来源的警报素细胞因子，可触发哮喘中的2型和非2型炎症 2 。 IBI3002具有高效的IL-4Rα和TSLP共同阻断功能。体外功能学实验显示比同靶点的已上市单克隆抗体更优。通过同时靶向IL-4Rα和TSLP，IBI3002具有抑制2型和非2型炎症的潜力，在抑制2型炎症方面具有潜在的协同作用，有望在治疗2型炎症性疾病中展现优效性。信达生物制药集团临床开发副总裁钱镭博士表示："在过去的几十年里，医疗界对哮喘的病理生理机制/表型和治疗选择的认知有了显著增加，特别是通过引入生物制剂治疗重度哮喘这一精准治疗的策略，为哮喘管理带来革命性的变革。高选择性药物通过靶向免疫炎症级联的特定步骤，有潜力进一步突破广大严重哮喘患者的治疗局限，并有望在多种重度哮喘炎症表型中实现最佳疾病控制；同时，我们也期待推进该分子未来在哮喘和其他多种炎症性疾病中的进一步开发。" 关于哮喘哮喘是一种由多种免疫细胞、细胞因子及炎症介质介导，累及全年龄段人群的异质性疾病，以喘息、气促、咳嗽和胸闷等多种症状为特征，与慢性气道炎症、可变的气流受限和气道高反应性相关 3 。根据2015年全球疾病负担（GBD）研究，约有3.58亿人患有哮喘 4 。根据气道或外周血细胞特征，哮喘可大致分为嗜酸性粒细胞性和非嗜酸性粒细胞性哮喘。嗜酸性粒细胞炎症主要由2型炎症驱动，包括2型辅助T细胞和2型固有淋巴细胞 5 。与嗜酸性粒细胞性哮喘相比，对于非嗜酸性粒细胞性哮喘的了解仍不充分 6 。高达10%的成人哮喘患者和2.5%的儿童哮喘患者患有重度哮喘 7 。尽管接受了足够的大剂量吸入治疗，重度哮喘患者仍存在症状持续或频繁急性加重，需要反复系统性糖皮质激素短期或维持治疗 8 。在这些患者中，需要给予额外治疗（可能包括生物制剂）以减轻疾病负担 2,3 。关于 IBI3002 IBI3002是一款全球首创靶向细胞表面IL-4Rα和警报素细胞因子TSLP的双特异性抗体。该分子具有高效的IL-4Rα和TSLP共同阻断功能。体外功能学实验显示比同靶点的已上市单克隆抗体更优。通过同时靶向IL-4Rα和TSLP，IBI3002具有治疗包括哮喘在内多种炎症性疾病的潜力。 IL-4是2型淋巴细胞分化的中心介质；它诱导产生2型相关细胞因子，如IL-5、IL-9、IL-13和/或2型相关趋化因子，如胸腺和活化调节趋化因子(TARC/CCL17)和嗜酸性粒细胞趋化因子-3。IL-4参与调节B细胞的同种型类别转换以产生血清IgE，并通过释放IL-5招募嗜酸性粒细胞。尽管IL-13在这些促炎过程中显示出一些冗余性，但它在介导杯状细胞增生、粘液产生、平滑肌收缩性和气道高反应性方面具有额外的作用。总的来说，IL-4和IL-13共同在2型炎症中起关键作用 1 。 TSLP是一种上皮细胞来源的警报素细胞因子，它在2型炎症诱导和通过IL-4、IL-5和IL-13产生的Th2细胞分化与成熟中占据上游位置。TSLP也被认为是哮喘中非2型炎症的触发因素 2 。关于信达生物 "始于信，达于行"，开发出老百姓用得起的高质量生物药，是信达生物的使命和目标。信达生物成立于2011年，致力于开发、生产和销售肿瘤、代谢及心血管、自身免疫、眼科等重大疾病领域的创新药物。公司已有10款产品获得批准上市，同时还有3个品种在NMPA审评中，4个新药分子进入III期或关键性临床研究，另外还有19个新药品种已进入临床研究。公司与海内外药企深入合作加速药物创新，与礼来、罗氏、赛诺菲、Adimab、Incyte和MD Anderson 癌症中心等国际合作方达成30多项战略合作。信达生物在不断开发创新药物、谋求自身发展的同时，始终心怀科学善念，坚守"以患者为中心"，心系患者并关注患者家庭，积极履行社会责任。信达生物希望和大家一起努力，提高中国生物制药产业的发展水平，以满足百姓用药可及性和人民对生命健康美好愿望的追求。详情请访问公司网站： www.innoventbio.com 或公司领英账号 www.linkedin.com/company/innovent-biologics/ 。声明：信达不推荐任何未获批的药品 / 适应症使用。前瞻性声明本新闻稿所发布的信息中可能会包含某些前瞻性表述。这些表述本质上具有相当风险和不确定性。在使用"预期"、"相信"、"预测"、"期望"、"打算"及其他类似词语进行表述时，凡与本公司有关的，目的均是要指明其属前瞻性表述。本公司并无义务不断地更新这些预测性陈述。这些前瞻性表述乃基于本公司管理层在做出表述时对未来事务的现有看法、假设、期望、估计、预测和理解。这些表述并非对未来发展的保证，会受到风险、不确性及其他因素的影响，有些乃超出本公司的控制范围，难以预计。因此，受我们的业务、竞争环境、政治、经济、法律和社会情况的未来变化及发展的影响，实际结果可能会与前瞻性表述所含资料有较大差别。参考文献： 1. Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production[J]. Cytokine, 2015, 75(1): 14-24. 2. Brusselle G G, Koppelman G H. Biologic therapies for severe asthma[J]. New England Journal of Medicine, 2022, 386(2): 157-171. 3. Global Initiative for Asthma. 2023 GINA Report, Global Strategy for Asthma Management and Prevention. 2023. 4. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet Respir Med. 2017 Oct;5(10 ):e30]. Lancet Respir Med. 2017;5(9):691-706. 5. Gans MD, Gavrilova T. Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes. Paediatr Respir Rev. 2020;36:118-127. 6. Israel E, Reddel H K. Severe and difficult-to-treat asthma in adults[J]. New England Journal of Medicine, 2017, 377(10): 965-976. 7. Settipane RA, Kreindler JL, Chung Y, Tkacz J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol 2019; 123(6): 564-572.e3. 8. Caminati M, Vaia R, Furci F, Guarnieri G, Senna G. Uncontrolled Asthma: Unmet Needs in the Management of Patients. J Asthma Allergy. 2021;14:457-466.

临床1期

2023-04-25

·GlobeNewswire-Health Care

ASLAN Pharmaceuticals Announces Four Abstracts on Eblasakimab and Farudodstat, Including Two Late-Breakers, to be Presented at the 1st International Societies for Investigative Dermatology Meeting

Late-breaking abstract on the differences between IL-13Rα1 and IL4R blockade on Type 2 and Type 1 signaling in atopic dermatitis (AD) accepted for oral presentation and late-breaking abstract on role of farudodstat in human model of alopecia areata accepted for poster presentation Abstracts of the two additional poster presentations at ISID have been published online in the Journal of Investigative DermatologySubgroup analysis from the previously published proof-of-concept study of eblasakimab in moderate-to-severe AD reveals that patients who received eblasakimab achieved higher improvements in EASI scores across different body regions, including the head and neck, compared to placebo Eblasakimab significantly inhibited cytokine-enhanced neuronal sensitization to itch and reduced spontaneous neuronal activity, suggesting a potential to treat conditions characterized by chronic itch and showing promise for broader application to neuropathic symptoms beyond itch SAN MATEO, Calif. and SINGAPORE, April 24, 2023 (GLOBE NEWSWIRE) -- ASLAN Pharmaceuticals (NASDAQ: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, today announced the acceptance of two late-breaker abstracts - one on eblasakimab and one on farudodstat – for presentation at the 1st International Societies for Investigative Dermatology (ISID) Meeting, which will take place from May 10 to 13, 2023, in Tokyo, Japan. Two further abstracts on eblasakimab, which were earlier accepted for presentation at the ISID meeting, have been published online in the Journal of Investigative Dermatology. “We are excited to be sharing three abstracts on eblasakimab at ISID, including a late-breaking podium presentation, as well as showcasing our new findings on farudodstat in an alopecia areata human ex vivo model,” said Dr Alex Kaoukhov, Chief Medical Officer at ASLAN Pharmaceuticals. “The abstracts published today highlight the potential of eblasakimab to offer important differentiated benefits for AD patients. Chronic itch is one of the most burdensome symptoms for AD patients and our translational data provide a strong mechanistic rationale for blocking IL-13Ra1 to combat cytokine-driven amplification of itch and spontaneous activation of neurons, potentially resulting in rapid itch relief for patients receiving eblasakimab treatment. Furthermore, a sub-analysis from our Phase 1 study indicated substantial improvements in EASI scores of eblasakimab-treated AD patients across all body areas, including sensitive, difficult-to-treat anatomical areas such as the head and neck, compared to placebo. These results suggest that in addition to addressing itch, eblasakimab may have the potential to treat sensitive areas of the skin where steroid-containing topical treatments are often restricted. Both of these attributes could provide substantial psychological relief to patients with AD. We look forward to learning more about the clinical benefits of eblasakimab on EASI and itch in patients from the topline data of our Phase 2 TREK-AD study in early July.” Late-breaker presentations Late-breaker oral presentation: Downstream effects of IL-13α1 blockade on Type 2 inflammation and Th1 immune axis activation in atopic dermatitis(abstract ID: LB1751) Pharmacology and Drug Development Mini-Symposium, May 13, 13:15-15:45 JST, Room CM18-04 Late-breaker poster presentation: A novel ex vivo model of human hair follicle immune privilege collapse reveals the potential of farudodstat, a DHODH inhibitor, as a therapeutic for alopecia areata treatment(abstract ID: LB1777) Additional details from the late-breaker abstracts will be shared after presentation at the conference and all posters presented at ISID will be made available within the “Publications” section of ASLAN’s website. 2023 ISID published abstracts Abstract 1 Eblasakimab monotherapy improves moderate-to-severe atopic dermatitis symptoms across anatomical regions in a Phase 1 study(abstract ID: 657) The clinical presentation of AD varies by anatomical location due to differences in skin area sensitivity and can limit an individual’s long-term treatment options. Current research shows that interleukin-4 (IL-4) and IL-13 signal through a Type 2 receptor complex composed of IL-4Rα1 and IL-13Rα1 to mediate the pathogenesis of AD. Eblasakimab obstructs this signaling cascade by binding to the IL-13Rα1 subunit. The Phase 1b subgroup analysis explored the effects of eblasakimab on Eczema Area and Severity Index (EASI) across different anatomical regions compared to placebo. Patients treated with 400mg or 600mg subcutaneous eblasakimab once weekly showed notable improvement in percent change from baseline in EASI across all four anatomic regions (head/neck, trunk, upper extremities, lower extremities) compared to placebo. The published abstract is available to view here. Abstract 2 Neuromodulation beyond itch is blocked by targeting IL-13Rα1 with eblasakimab(abstract ID: 1594) IL-4 and IL-13, two cytokines that play a pivotal role in the pathogenesis of AD, are associated with high-burden symptoms such as chronic itch. IL-13 signals via the IL-13Rα1 subunit to enhance histaminergic and nonhistaminergic itch. Eblasakimab binds to the IL-13Rα1 subunit to block IL-4 and IL-13 signalling pathways. This study evaluated 1) whether IL-4 and IL-13 exert redundant or distinct functions in human sensory neurons, and whether eblasakimab can 2) attenuate cytokine-enhanced neuronal responses to itch and 3) reduce spontaneous neuronal activity. Human dorsal root ganglia neurons were treated with IL-4, IL-13, or their combination with or without eblasakimab and subsequently either challenged with pruritogens (BAM8-22 and PAMP-20) or tested for spontaneous neuronal activity. Neuronal responses to pruritogens and spontaneous neuronal activity were measured via live-cell calcium imaging. When applied to human dorsal root ganglion, IL-4, IL-13, and their combination treatments enhanced neuronal responses to the non-histaminergic pruritogen (BAM-822) and IL-13 treatment increased neuronal responses to the histaminergic pruritogen (PAMP-20) through amplifications of the activity of MRGPRX2, suggesting a novel neuroimmune pathway besides its mast cell specific function. Eblasakimab significantly hampered cytokine-enhanced itch responses to both pruritogens. Compared to vehicle, IL-4 treatment significantly increased spontaneous neuronal activity; this effect was notably reduced by eblasakimab. Spontaneous neuronal activity was not impacted by IL-13 treatment but was increased with IL-4 treatment, which was also effectively reduced by eblasakimab. These results reveal that IL-4 and IL-13 exert nonredundant neuronal function and demonstrate the ability of eblasakimab to block these effects. This indicates that direct impact on neuronal responses may contribute to reduction of chronic itch demonstrated in AD patients treated with eblasakimab. The published abstract is available to view here. About eblasakimab Eblasakimab is a potential first-in-class monoclonal antibody targeting the IL-13 receptor subunit of the Type 2 receptor, a key pathway driving several allergic inflammatory diseases. Eblasakimab’s unique mechanism of action enables specific blockade of the Type 2 receptor and has the potential to improve upon current biologics used to treat allergic disease. By blocking the Type 2 receptor, eblasakimab prevents signaling through both interleukin 4 (IL-4) and interleukin 13 (IL-13) – the key drivers of inflammation in atopic dermatitis (AD). Positive results from a Phase 1b multiple-ascending-dose study established proof-of-concept for eblasakimab and supported its potential as a novel, differentiated treatment for AD. ASLAN is currently conducting TREK-AD, a Phase 2b trial to evaluate eblasakimab in biologic naïve moderate-to-severe AD patients, with topline readout expected in early July 2023. ASLAN is also investigating eblasakimab in dupilumab experienced, moderate-to-severe AD patients in the Phase 2 trial TREK-DX, with data expected in the first quarter of 2024. About farudodstat Farudodstat is a potent, oral DHODH inhibitor that suppresses immune cell proliferation and IFN-γ secretion by blocking de novo production of pyrimidines required for DNA replication. Compared to first-generation DHODH inhibitors, farudodstat has been shown to be approximately 30 times more potent in its inhibition of DHODH and limiting T cell activity and has demonstrated a well-tolerated safety profile. ASLAN has generated data showing that farudodstat can protect against the loss of immune privilege in hair follicles, supporting its potential as a first-in-class treatment option for alopecia areata (AA). About ASLAN Pharmaceuticals ASLAN Pharmaceuticals (Nasdaq: ASLN) is a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients. ASLAN is developing eblasakimab, a potential first-in-class antibody targeting the IL-13 receptor in moderate-to-severe atopic dermatitis (AD) with the potential to improve upon current biologics used to treat allergic disease. Eblasakimab is being investigated in a global Phase 2b trial of moderate-to-severe AD patients with topline readout expected in early July 2023. ASLAN is also developing farudodstat, a potent oral inhibitor of the enzyme DHODH, as a potential first-in-class treatment for alopecia areata (AA) and plans to initiate a proof-of-concept trial in 2Q 2023. ASLAN has teams in San Mateo, California, and in Singapore. For additional information please visit the website or follow ASLAN on LinkedIn. Forward looking statements This release contains forward-looking statements. These statements are based on the current beliefs and expectations of the management of ASLAN Pharmaceuticals Limited and/or its affiliates (the "Company"). These forward-looking statements may include, but are not limited to statements regarding the Company’s business strategy and clinical development plans; the Company’s plans to develop and commercialize eblasakimab and farudodstat; the safety and efficacy of eblasakimab and farudodstat; the Company’s plans and expected timing with respect to clinical trials, clinical trial enrolment and clinical trial results for eblasakimab and farudodstat; the potential of eblasakimab as a first-in-class treatment for atopic dermatitis and of farudodstat as a first-in-class treatment for alopecia areata; and the Company’s cash runway. The Company’s estimates, projections and other forward-looking statements are based on management's current assumptions and expectations of future events and trends, which affect or may affect the Company’s business, strategy, operations, or financial performance, and inherently involve significant known and unknown risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of many risks and uncertainties, which include, unexpected safety or efficacy data observed during preclinical or clinical studies; clinical site activation rates or clinical trial enrolment rates that are lower than expected; the impact of the COVID-19 pandemic or the ongoing conflict between Ukraine and Russia and bank failures on the Company’s business and the global economy; general market conditions; changes in the competitive landscape; and the Company’s ability to obtain sufficient financing to fund its strategic and clinical development plans. Other factors that may cause actual results to differ from those expressed or implied in such forward-looking statements are described in the Company’s US Securities and Exchange Commission filings and reports (Commission File No. 001- 38475), including the Company’s Annual Report on Form 20-F filed with the US Securities and Exchange Commission on March 24, 2023. All statements other than statements of historical fact are forward-looking statements. The words “believe,” “may,” “might,” “could,” “will,” “aim,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “plan,” or the negative of those terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify estimates, projections, and other forward-looking statements. Estimates, projections, and other forward-looking statements speak only as of the date they were made, and, except to the extent required by law, the Company undertakes no obligation to update or review any estimate, projection, or forward-looking statement. Media and IR contacts Emma Thompson Spurwing Communications Tel: +65 6206 7350 Email: ASLAN@spurwingcomms.com Ashley R. Robinson LifeSci Advisors, LLC Tel: +1 (617) 430-7577 Email: arr@lifesciadvisors.com

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100 项与 Binetrakin 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D03117	-	-	DB12182

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性淋巴细胞白血病	临床2期	-	Merck Sharp & Dohme Corp.	-
胃肠道肿瘤	临床2期	-	Merck Sharp & Dohme Corp.	-
炎症	临床2期	-	Merck Sharp & Dohme Corp.	-
非小细胞肺癌	临床2期	-	Merck Sharp & Dohme Corp.	-
类风湿关节炎	临床2期	-	Merck Sharp & Dohme Corp.	-
免疫缺陷综合征	临床1期	-	Merck Sharp & Dohme Corp.	-

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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


AAAAI2007	N/A	-	120	Interleukin-4	蓋齋壓衊鑰鬱襯衊廠壓(鑰淵顧遞窪獵鹽夢餘鹽) = 鹹鏇夢夢壓鏇餘醖壓夢憲顧網顧衊艱鏇襯獵積 (繭願鏇壓願鬱淵範壓製 )	-	2007-01-01
				Interleukin-4	蓋齋壓衊鑰鬱襯衊廠壓(鑰淵顧遞窪獵鹽夢餘鹽) = 襯壓醖遞糧衊膚糧簾鬱憲顧網顧衊艱鏇襯獵積 (繭願鏇壓願鬱淵範壓製 )