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

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.

LRG 1是一种分泌型糖蛋白，通过促进血管功能障碍、纤维化和不受控制的细胞增殖，在一系列高度流行的慢性疾病中发挥关键作用。越来越多的证据表明，它参与疾病，如慢性肾脏疾病（CKD），影响全球8亿多人，发病率和死亡率很高，以及几种巨大未满足需求的实体癌，其中不受控制的细胞增殖和血管和免疫功能障碍导致严重恶化的结果。LRG 1 LTD，交易名称为 **Senya Therapeutics**，正在开发针对LRG 1的专有生物制剂，为这些关键疾病人群提供治疗干预。迄今为止，该公司已经开发出一种抑制LRG 1活性的先导分子STX-002，并已在包括非人灵长类动物在内的一系列转化临床前模型中成功证明了其有效性和安全性。这些结果表明，该化合物是安全的，耐受性良好，我们的方法可用于治疗疾病，通过血管正常化，减缓纤维化，并改善稳态microenvironment.This项目的重点是STX-002，人源化铰链稳定的IgG 4功能阻断抗体。该项目旨在确认STX-002的肾脏适应症，并为所选适应症制定患者选择标准。对于肿瘤学，该项目旨在获得数据，以支持针对具有高免疫逃避风险和高水平LRG 1的患者以及在新辅助治疗环境中使用STX-002的篮子试验的启动。该项目还计划提供GMP开发和IND计划。这项工作将在伦敦（帝国）、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进行，由思想领袖临床医生合作，他们将访问存档活检材料并分析样本和相关患者数据。CMC开发和IND前计划将与一家在CMC和IND支持工作方面具有专业知识的英国供应商共同开发。最后，该项目还包括基于STX-002的治疗的卫生经济学评估，其结果将有助于指导临床开发策略和支持未来的投资决策。这些工作包的结果对于完善STX-002的治疗假设和制定明确的临床阶段路径至关重要。因此，该计划的产出将大大提高A系列加薪的准备程度。Senya设想用STX-002治疗CKD和免疫耐药实体瘤将解决这些疾病领域大量未满足的需求。