IL1RAP

LUND, SWEDEN / ACCESSWIRE / April 2, 2024 / Cantargia (STO:CANTA) Cantargia (Cantargia AB; Nasdaq Stockholm:CANTA) today reported publication of promising preclinical data supporting the potential of the anti-IL1RAP antibody CAN10 as treatment of atherosclerosis. The data, published in the journal ‘Cardiovascular Research', shows that IL1RAP-blockade reduced the development of atherosclerotic plaques as well as reduced the plaque inflammation. Atherosclerosis is a huge future opportunity within the CAN10 project. "CAN10 is currently investigated in a phase I clinical trial, following promising effects in a number of disease models of autoimmunity or inflammatory diseases. Atherosclerosis is one such disease with a very high medical need that affect a vast number of patients and the publication in a high impact journal underscores the interest and potential of CAN10 outside its lead indications myocarditis and systemic sclerosis" said Göran Forsberg, CEO of Cantargia . Atherosclerosis is the main underlying cause of cardiovascular disease, including heart attack and stroke, and the leading cause of death in western societies. It is a chronic inflammatory vascular disease characterized by atherosclerotic plaque formation in the arterial wall. A high degree of inflammation in the atherosclerotic plaque is associated with an increased risk of heart attack and stroke, and molecules involved in plaque inflammation are therefore considered important therapeutic targets. The published data demonstrate that IL1RAP may be one such promising target that is expressed on various inflammatory cells in the atherosclerotic plaques. Therapeutic treatment with a CAN10 surrogate antibody resulted in a significant reduction in plaque burden and a reduced plaque inflammation, through both attenuated accumulation of inflammatory cells as well as a reduced expression of inflammatory mediators in the plaques of mCAN10 treated mice. Collectively, this strongly suggests that CAN10 treatment can have a positive effect on atherosclerosis and plaque inflammation, supporting the notion that IL1RAP represents a novel therapeutic target in this disease. These data were generated in collaboration with Dr. Daniel Engelbertsen's research group at Lund University. Key data from these studies have previously been presented as a poster at the European Atherosclerosis Society Congress in 2022. The article, titled "IL1RAP blockade limits development of atherosclerosis and reduces plaque inflammation", is authored by Mulholland et al. and is available via the following link . About Cantargia Cantargia AB (publ), reg. no. 556791-6019, is a biotechnology company that develops antibody-based treatments for life-threatening diseases and has established a platform based on the protein IL1RAP, involved in a number of cancer forms and inflammatory diseases. The main program, the antibody nadunolimab (CAN04), is being studied clinically primarily in combination with chemotherapy with a focus on pancreatic cancer, non-small cell lung cancer and triple-negative breast cancer. Positive interim data for the combinations indicate stronger efficacy than would be expected from chemotherapy alone. Cantargia's second development program, the antibody CAN10, blocks signaling via IL1RAP in a different manner than nadunolimab and addresses treatment of serious autoimmune/inflammatory diseases, with initial focus on systemic sclerosis and myocarditis. Cantargia is listed on Nasdaq Stockholm (ticker: CANTA). More information about Cantargia is available at . About CAN10 The CAN10 antibody binds strongly to its target IL1RAP and has a unique capability to simultaneously inhibit signaling via IL-1, IL-33 and IL-36. Inhibition of these signals can be of significant value in the treatment of several inflammatory or autoimmune diseases. The initial focus of CAN10 will be on two severe diseases: myocarditis and systemic sclerosis. In preclinical in vivo models of myocarditis, a CAN10 surrogate antibody significantly reduced the development of inflammation and fibrosis, and significantly counteracted the deterioration of the cardiac function. The CAN10 surrogate also inhibited disease development in models of systemic sclerosis, psoriasis, psoriatic arthritis, atherosclerosis and peritonitis. A clinical phase I study, investigating CAN10 in healthy volunteers and psoriasis patients, is ongoing. Up to 80 subjects may be included in the trial, the first clinical data set shows good safety. Additional data from the trial are expected continuously during 2024. Attachments Cantargia publishes data highlighting the potential of CAN10 in atherosclerosis SOURCE: Cantargia View the original press release on accesswire.com

LUND, SWEDEN / ACCESSWIRE / March 27, 2024 / Cantargia (STO:CANTA) Cantargia (Cantargia AB; Nasdaq Stockholm: CANTA) today reported on the progress in the upcoming phase Ib/IIa clinical trial investigating nadunolimab in up to 40 patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). This trial is financed through a grant from the US Department of Defense (DOD). With the upcoming submission to the US FDA, the current plan is to commence the trial during the summer of 2024, pending regulatory approval. "Besides the exciting results generated with nadunolimab in patients with solid tumors, the prestigious grant from the DOD validates the additional potential in leukemia. We are really excited to start treating patients within a few months and look forward to this important clinical trial" said Göran Forsberg, CEO of Cantargia. Nadunolimab has been investigated to date by Cantargia in approximately 300 patients with solid tumor indications and has shown clear signals of clinical activity. Right now, a controlled phase II clinical trial in triple negative breast cancer is ongoing and a new phase IIb trial investigating two dose levels of nadunolimab and one control group in first line treatment of metastatic pancreatic cancer is currently in the start-up phase. In the context of cancer, IL1RAP was initially discovered as a therapeutic target in leukemia. Preclinical and translational results on IL-1 biology in various forms of leukemia as well as an overexpression of IL1RAP on both leukemia cells and leukemic stem cells indicate that nadunolimab has the potential to be used in the treatment of several different forms of the disease. The new phase Ib/IIa clinical trial is designed to investigate nadunolimab monotherapy as well as combination therapy, in up to 20 patients with AML and 20 with MDS. In addition to investigating anticancer effects, the study will include an extensive package of biomarker assessments using blood and bone marrow samples, including single cell multimodal analysis. The trial is sponsored by a grant from the DOD to The University of Texas MD Anderson Cancer Center which will be responsible for conducting the trial, with Dr Gautam Borthakur as principal investigator. More details on the trial will be disclosed once the trial has received regulatory approval from the US FDA and relevant IRB. About Cantargia Cantargia AB (publ), reg. no. 556791-6019, is a biotechnology company that develops antibody-based treatments for life-threatening diseases and has established a platform based on the protein IL1RAP, involved in a number of cancer forms and inflammatory diseases. The main program, the antibody nadunolimab (CAN04), is being studied clinically primarily in combination with chemotherapy with a focus on pancreatic cancer, non-small cell lung cancer and triple-negative breast cancer. Positive interim data for the combinations indicate stronger efficacy than would be expected from chemotherapy alone. Cantargia's second development program, the antibody CAN10, blocks signaling via IL1RAP in a different manner than nadunolimab and addresses treatment of serious autoimmune/inflammatory diseases, with initial focus on systemic sclerosis and myocarditis. Cantargia is listed on Nasdaq Stockholm (ticker: CANTA). More information about Cantargia is available at . About nadunolimab (CAN04) The antibody nadunolimab binds strongly to its target IL1RAP and functions by inducing ADCC and blocking IL-1alpha and IL-1beta signaling. Nadunolimab can thereby counteract the IL-1 system which contributes to the immune suppressive tumor microenvironment and development of resistance to chemotherapy. Nadunolimab is investigated in multiple clinical trials; the phase I/IIa trial CANFOUR, NCT03267316, evaluates nadunolimab in combination with standard chemotherapies in patients with PDAC (gemcitabine/nab-paclitaxel) or NSCLC (platinum-based chemotherapies). Positive interim data show durable responses for the combination therapy in 73 PDAC patients, resulting in median iPFS of 7.2 months and median OS of 13.2 months. An even higher median OS of 14.2 months was observed in a subgroup of patients with high tumor levels of IL1RAP. Strong efficacy was also observed in 30 NSCLC patients with median PFS of 7.0 months and a response rate of 53%; even higher responses were observed in non-squamous NSCLC patients. Early efficacy data from the phase Ib/II trial TRIFOUR, NCT05181462, also shows signs of promising efficacy in TNBC with a 60% response rate for nadunolimab combined with carboplatin/gemcitabine. Nadunolimab is also investigated with chemotherapy in the clinical trials CAPAFOUR, NCT04990037, and CESTAFOUR, NCT05116891, and with the checkpoint inhibitor pembrolizumab in the CIRIFOUR trial, NCT04452214. Attachments Cantargia reports progress towards start of DOD-sponsored clinical trial of nadunolimab in leukemia SOURCE: Cantargia View the original press release on accesswire.com

注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。20世纪70年代开始，印度制药产业开始崛起，当前印度已经是名副其实的仿制药大国，在之前介绍过不少印度药企，今天想和大家聊聊该国的TOP10药企——Glenmark Pharmaceuticals（以下简称Glenmark），Glenmark成立于1977年，致力于在皮肤科、呼吸系统和肿瘤学领域建立品牌药、仿制药和OTC的全球业务，同时还在糖尿病、心血管和口服避孕药等其他治疗领域拥有一系列产品。公司旗下包括Glenmark life science（GLS）和Ichnos Glenmark Innovation（IGI）两个子公司。其中Glenmark life science成立于2019年，在全球主要市场制造和销售API（活性药物成分），目前有接近140个产品，全球前20仿制药企业均是其客户。作为高质量原料药的领先生产商，还为许多跨国和专业制药公司提供CDMO服务，为客户提供定制的解决方案，包括支持监管申请、研究、技术援助和专业API的制造。2023年9月，Glenmark宣布与Nirma Limited达成最终协议，剥离GLS 75%的股份，经过此交易后，Glenmark持有GLS 7.84%的股份。Ichnos Glenmark Innovation（IGI）专注于肿瘤治疗药物的研发，目前拥有三种处于临床阶段的针对多发性骨髓瘤、急性髓系白血病和实体瘤的创新肿瘤分子。该公司的主要优势在于其专有的BEAT蛋白工程平台，该平台能够创造出高度灵活和可制造的全长多特异性抗体，通过利用这个平台，公司的目标是发现能够同时针对多个因素的化合物，从而扩大它们的管线并产生长期价值。2024年1月底，Glenmark宣布与其子公司Ichnos Sciences成立联盟-Ichnos Glenmark Innovation（IGI），该联盟将Glenmark在小分子方面的研发能力与Ichnos Sciences在新型生物制剂方面的研发能力结合，以继续开发治疗血液系统恶性肿瘤和实体瘤的治疗方案。位于仿制药企林立的印度，Glenmark打算涉足艰难的创新药赛道，在公司长期发展战略中，公司决定集中其创新力量将公司从一家仿制药企业发展为一家具有多样化先进药物组合的综合型全球制药公司。当前研发管线专注于肿瘤和自身免疫性疾病01 主打产品药融云数据（www.pharnexcloud.com）显示：Glenmark针对呼吸系统疾病的主要产品包括Indame DPI（用于治疗哮喘）、VirX Nasal Spray（用于预防呼吸道感染的鼻喷雾剂）、Airz FB（用于慢性阻塞性肺病）、Pirfenidone（治疗特发性肺纤维化）、Ipratropium（可用于扩大肺部气道）、Ascroil Expectorant（用于治疗咳嗽）、Aerogold（用于治疗支气管痉挛）、Glemont tablet（用于治疗哮喘和过敏）和Ryaltris（糠酸莫米松+盐酸奥洛他定）。皮肤病类产品主要包括Candid Prickly Heat Powder（用于控制细菌生长和感染）、Minym Gel（用于治疗痤疮）、La Shield Probiotic Moisturizer（保湿霜）、Isavuconazole（用于治疗真菌感染）、Lasderma Cream（针对色素沉淀并有提亮功效）、Tacroz（用于治疗特应性湿疹）、Momate Ointment（治疗皮肤湿疹和牛皮藓）、Powercort Cream（治疗特应性皮炎和牛皮藓）和Fenismart gel（用于缓解皮肤瘙痒和皮疹等）。肿瘤学领域产品包括Abiraterone（阿比特龙）、Sunitinib（舒尼替尼）、Pazopanib（培唑帕尼）等，另外还有针对糖尿病和心脏领域的产品。药融云数据（www.pharnexcloud.com）显示：其中，Ryaltris作为公司第一个全球产品，目前已在70多个国家/地区提交上市申请，这是一种创新的鼻腔喷雾剂，由糠酸莫米松和盐酸奥洛他定固定剂量组合而成，2022年1月获FDA批准，用于治疗12岁及以上的成人和儿童患者的季节性过敏性鼻炎。2019年2月，远大医药与Glenmark签订独家授权协议，获得商业化Ryaltris的独家授权和为期20年的中国独家专利权，2024年2月20日，远大医药宣布用于治疗成人和儿童过敏性鼻炎(AR)的全球创新药Ryaltris复方鼻喷剂(GSP 301 NS)向国家药监局递交的新药上市申请已获受理。目前Glenmark还专注于加强与Bausch、Hikma和Menarini等主要合作者的合作伙伴关系，以在新的地区将该产品商业化。药融云数据库：药品基本信息除了以上提到的产品外，API也是公司的营收大头，以下是公司部分API清单：02 研发管线Glenmark当前正在进展的研发管线包括肿瘤学和自身免疫性疾病的产品，各管线具体进展情况如下：1、肿瘤学（1）ISB 1442ISB 1442是一种靶向CD38和CD47的first-in-class双特异性抗体，由Ichnos实验室的科学家研发，通过抑制CD47-SIRPα轴来杀死表达CD38的肿瘤细胞，以增加抗体依赖性细胞吞噬作用（ADCP）并增强抗体依赖性细胞毒性（ADCC）以及补体依赖性细胞毒性（CDC）。2023年3月ISB 1442被FDA授予多发性骨髓瘤孤儿药资格，目前研究进行到临床试验1期。从2023年介绍的临床试验1期的信息来看，ISB1442治疗耐受性良好，观察到的CRS事件为低级别（1或2次），大多在一天内消退，迄今为止，尚未观察到神经毒性事件且没有感染或贫血的信号。同时，公司还计划开发ISB1442用于急性髓系白血病（AML），研究表明，通过多种抗体依赖性作用机制杀伤测定来衡量，ISB1442在CD38高/低肿瘤模型中相对于达雷妥尤单抗的体外效力更高。（达雷妥尤单抗是全球获批的首个针对肿瘤浆细胞表面的CD38分子、人源化免疫球蛋白IgG1单克隆抗体。最初由丹麦药企Genmab研发的，2012年强生通过签署11亿美元的协议从Genmab获得其全球独家权利）（2）ISB 2001ISB 2001是first-in-class的靶向多发性骨髓瘤细胞上BCMA和CD38的T细胞结合抗体，它是一种基于Ichnos专有BEAT平台的三特异性抗体，可实现全长多特异性抗体的最大灵活性和出色的可制造性。目前正在进行ISB2001针对复发/难治性多发性骨髓瘤患者的临床试验1期、首次人体剂量递增和剂量扩展研究。首位患者于2023年11月给药，目前正在积极招募队列4的患者。体外研究表明，与目前被批准用于治疗多发性骨髓瘤或正在进行临床研究中测试的所有测试抗体相比，ISB 2001对肿瘤细胞的杀伤力更高。多发性骨髓瘤模型的体内研究也表明，与批准的多发性骨髓瘤抗体治疗相比，ISB 2001的效力更高。2023年4月，Ichnos获得了FDA和澳大利亚HREC的批准，启动了ISB 2001用于治疗复发/难治性多发性骨髓瘤的临床试验1期首次人体研究，公司正在考虑同时将临床研究扩展到其他国家。（3）GRC 54276GRC 54276是一种HPK1抑制剂，目前正在开发作为实体瘤患者的口服IO（免疫肿瘤学）辅助治疗药物。造血祖细胞激酶1（HPK1）是T细胞和B细胞受体信号转导的负调节因子，是一种有吸引力的癌症免疫肿瘤治疗策略。GRC 5427作为一种新型的口服活性HPK1抑制剂，具有独立的疗效，可增强目前的免疫治疗效果，目前正在首次人体临床试验1期研究中对其进行评估。自2022年7月以来，该研究的临床试验1a期单药治疗阶段在印度进行。该研究的50 mg单药疗法回填队列正在招募其他受试者，以进一步评估GRC 54276单药疗法的安全性和耐受性。GRC 54276与帕博利珠单抗和阿替利珠单抗的临床试验1b期联合研究分别于24财年第一季度和24财年第二季度在印度和美国启动。截至24财年第三季度，GRC 54276与帕博利珠单抗和阿替利珠单抗的两个剂量队列已经完成，第三个队列的患者招募和给药正在进行中。2、炎症和自身免疫性疾病公司目前有两项针对自身免疫性疾病的单克隆抗体候选药物处于研发阶段，具体进展情况如下：抗体ISB 830（telazorlimab），ISB 830是一种OX40拮抗剂，在2021年完成了一项针对中度至重度特应性皮炎的临床试验2b期研究。2023年10月Ichnos与Astria Therapeutics签订了ISB 830治疗自身免疫性疾病的独家全球许可协议。ISB 880是一种阻断IL-1RAP信号转导的全人源、高亲和力单克隆抗体，已完成针对自身免疫性疾病患者的IND研究，目前正在进行临床试验1期研究。2021年12月与Almirall签订了ISB 880治疗自身免疫性疾病的独家全球许可协议。根据协议条款，Almirall承担该化合物的全球开发和商业化的全部成本和责任。财务状况Glenmark 2023-2024财年前三季度（2023.04-2023.12）综合运营收入为981.91亿卢比（11.97亿美元），上年同期为961.64亿卢比（12.08美元），同比增长2.9%。2023-2024财年第三季度综合运营收入290.96亿卢比（3.491亿美元），而去年同期为346.39亿卢比（4.226亿美元），同比下降16%，这一季度销售额下降的主要原因是公司的印度业务受到了较大影响，因为公司通过整合库存点和合理化渠道库存，对其整体分销模式进行了调整，这将有助于该公司在未来提高营业利润率和整体营运资本。（注：2023-2024财年数据根据汇率1.00美元=82.69印度卢比换算，2022-2023财年数据根据汇率1.00美元=79.58印度卢比换算）2023-2024财年第三季度财政营收分区域来看，印度配方业务销售额为26.22亿卢比（2080万美元），上年同期为107.45亿卢比（1.307亿美元），下降了75.6%；北美业务的成品制剂销售收入为76.29亿卢比（9160万美元），上年同期83.73亿卢比（1.023亿美元），同比下降8.9%；欧洲业务收入63.57亿卢比（7640万美元），与上年同期相比增长了28.9%；其他地区收入72.50亿卢比（8720万美元），与上年同期相比增长10.8%；GLS的API产品销售额为41.29亿卢比（4960万美元），与上年同期相比增长9.9%。以下是该季度公司全球产品Ryaltris在主要地区的市场份额情况：2022-2023财年，Glenmark的综合运营收入为1299.01亿卢比（16.19亿美元），与上年同期相比增长5.6%。根据IQVIA MAT 2023年3月的数据，Glenmark在印度制药市场的呼吸系统细分市场中排名第二，与整个呼吸系统市场相比，价值增长高出1.5倍。整体来看，Glenmark现在在印度的皮肤科和呼吸科领域均排名第二。国内合作最新动态药融云数据（www.pharnexcloud.com）显示：2024年1月25日，康宁杰瑞与思路迪医药共同宣布，双方就皮下注射PD-L1抗体药物恩维达（恩沃利单抗注射液）与Glenmark全资附属公司Glenmark Specialty S.A.达成协议，授予Glenmark在印度、亚太地区（除新加坡、泰国、马来西亚）、中东和非洲、俄罗斯、独联体和拉丁美洲的肿瘤适应症开发和商业化独家许可权益。有关KN035开发及商业化费用由Glenmark自行承担。恩维达由康宁杰瑞自主研发，2020年康宁杰瑞、思路迪医药、先声药业三方达成战略合作，康宁杰瑞作为原研方负责生产和质量，思路迪医药负责肿瘤领域的临床开发，先声药业负责产品在中国大陆的独家商业推广。2021年11月，恩维达在中国率先获批上市，适用于不可切除或转移性微卫星高度不稳定(MSI-H)或错配修复基因缺陷型(dMMR)的成人晚期实体瘤患者的治疗，包括既往经过氟尿嘧啶类、奥沙利铂和伊立替康治疗后出现疾病进展的晚期结直肠癌患者以及既往治疗后出现疾病进展且无满意替代治疗方案的其他晚期实体瘤患者。目前在中国和国外多个地区针对多个肿瘤适应症开展研究。参考：NMPA/CDE药融云数据，www.pharnexcloud.comFDA/EMA/PMDA；相关公司公开披露（除标注外，正文图片均来自企业官网）；https://glenmarkpharma.com/；https://www.cphi.cn/news/show-wiki-195214.html；https://www.grandpharm.com/news/%e8%bf%9c%e5%a4%a7%e5%8c%bb%e8%8d%af%e5%85%a8%e7%90%83%e5%88%9b%e6%96%b0%e4%ba%a7%e5%93%81ryaltris%e5%a4%8d%e6%96%b9%e9%bc%bb%e5%96%b7%e5%89%82%e5%9b%bd%e5%86%85nda%e8%8e%b7%e5%9b%bd%e5%ae%b6/；https://xueqiu.com/4376152234/276426105；等等。本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐 活动推荐  5月底 • 第八届大湾区生物医药创新者峰会  关键词：  小分子，XDC，多肽及GLP-1热点话题，80+行业专家（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。