Indication selection, patient stratification, and IND preparation for STX-002: the first-in-class LRG1 inhibitor for treatment of chronic kidney disease and immunotherapy-resistant tumours.

STX-002的适应症选择、患者分层和IND准备：用于治疗慢性肾病和免疫治疗耐药肿瘤的一流LRG1抑制剂。

• 批准号: 10092585
• 金额: $ 86.58万
• 依托单位: LRG1 LTD
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10092585
• 关键词: Indication; selection; patient; stratification; IND; Indication; selection; patient; stratification; IND

LRG1 is a secreted glycoprotein that plays a key role in a range of highly prevalent chronic diseases by promoting vascular dysfunction, fibrosis and uncontrolled cell proliferation. Mounting evidence shows its involvement in diseases such as chronic kidney disease (CKD) which affects over 800 million people globally with significant morbidity and mortality, and several solid cancers of enormous unmet need, in which uncontrolled cell proliferation and vascular and immune dysfunction contribute to substantially worse outcomes.LRG1 LTD, trading as **Senya Therapeutics**, is developing proprietary biologics targeting LRG1 to provide therapeutic interventions in these key disease populations. To date, the company has developed a lead molecule, STX-002, that inhibits the activity of LRG1 and has successfully demonstrated its efficacy and safety in a range of translational preclinical models including non-human primates. These results have shown that the compound is safe and well-tolerated, and that our approach can be used to treat disease through vascular normalisation, deceleration of fibrosis, and an improved homeostatic microenvironment.This project focuses on STX-002, a humanised hinge-stabilised IgG4 function-blocking antibody. The project aims to confirm the nephrology indications for STX-002 and generate patient selection criteria for the chosen indications. For oncology, the project aims to gain data to support initiation of a basket trial for patients with high risk of immune evasion and high levels of LRG1 and for the use of STX-002 in neoadjuvant settings. The project also plans to deliver GMP development and IND plans. The work will be conducted at clinical and biomedical research centres in London (Imperial), Edinburgh (University) and Amsterdam (Netherlands Cancer Institute (NKI)) with thought-leader clinician collaborators who will access archival biopsy material and analyse the samples and related patient data. The CMC development and pre-IND plan will be co-developed with a UK-based vendor with expertise in CMC and IND-enabling work. Finally, the project also includes health economic assessment of STX-002-based treatment, result of which will help guide clinical development strategy and support future investment decisions.The results of these work packages are crucial for refining the therapeutic hypothesis of STX-002 and developing a clear path to the clinical stage. The output from this program therefore will significantly enhance the readiness for Series A raise. Senya envisages that treatment of CKD and immunotherapy-resistant solid tumours with STX-002 will address substantial unmet needs in these disease areas.

LRG1是一种分泌的糖蛋白，通过促进血管功能障碍，纤维化和不受控制的细胞增殖，在一系列高度普遍的慢性疾病中起关键作用。越来越多的证据表明，它参与了诸如慢性肾脏疾病（CKD）等疾病，这些疾病在全球范围内影响超过8亿人，具有明显的发病率和死亡率，以及几种巨大未满足需求的固体癌症，未经控制的细胞增殖，血管和免疫功能障碍在实质上造成了较差的较差的范围，从而导致了与众不同。针对LRG1的生物制剂在这些关键疾病人群中提供治疗性干预措施。迄今为止，该公司已经开发了一个铅分子STX-002，该分子抑制了LRG1的活性，并在包括非人类灵长类动物在内的一系列翻译临床前模型中成功证明了其功效和安全性。这些结果表明，该化合物是安全且耐受良好的，并且我们的方法可用于通过血管归一化，纤维化减速和改善的稳态微环境来治疗疾病。该项目侧重于STX-002，这是一个人性化的铰链铰链稳定的IgG4功能阻断抗体。该项目旨在确认STX-002的肾脏科指征，并为所选指示生成患者选择标准。对于肿瘤学，该项目旨在获取数据，以支持对高逃避和高水平LRG1以及在新辅助环境中使用STX-002的患者的篮子试验开始。该项目还计划提供GMP开发和IND计划。这项工作将在伦敦，爱丁堡（大学）和阿姆斯特丹（荷兰癌症研究所（NKI））的临床和生物医学研究中心与思想领袖临床合作者一起进行，他们将访问档案活检材料并分析样品和相关患者数据。 CMC开发和预先计划将与一家英国供应商共同开发，该供应商在CMC和索引工作方面具有专业知识。最后，该项目还包括对基于STX-002的治疗的健康经济评估，其结果将有助于指导临床开发策略并支持未来的投资决策。这些工作包的结果对于完善STX-002的治疗假设至关重要，并为临床阶段开发清晰的途径。因此，该程序的产出将大大提高A系列升高的准备。 Senya设想，用STX-002治疗CKD和免疫疗法的实体瘤将满足这些疾病区域的实质性未满足需求。