Treatment of Inflammatory Complications of Respiratory Infection

摘要 瑞斯帕纳治疗公司正在开发一种专利的一流治疗性单抗(MAb)，RT- 002，用于治疗与急性呼吸道相关的虚弱且往往是致命的炎症并发症 条件。我们已经确定了一个领先的候选者，RT-002，以及一个同样有希望的替代品。RT-002靶标 表面活性蛋白A受体SP-R210，一个宿主介导的靶标，无论如何都有疗效的希望 病原体的进化。 严谨的活体小鼠研究表明，不仅死亡率降低，而且肺功能恢复 健康也是如此。此外，RT-002不针对单个细胞因子途径，该途径可能具有 负面影响。因此，RT-002有可能填补流感治疗药物的一项重大空白。 由于最广泛使用的工具是预防感染的疫苗和阻止感染的抗病毒药物；然而， 这些都受到部分疗效、疫苗迟疑和出现抗药性的限制。 该第二阶段计划的目标是继续开发RT-002和备份，目标是 以尽可能快和有效的方式将治疗方法推向临床试验。具体地说，目标是 包括：1)通过我们的功能免疫表型确定RT-002在人体血液中的药理作用 识别人体血液中RT-002靶点参与和免疫激活的检测将为治疗提供信息 减轻危重病患者异常免疫激活的设计；2)建立其药理活性 RT-002利用人源化FcRN小鼠治疗严重流感建立了安全性、毒性、 药效学、剂量、计划和治疗持续时间，以降低RT-002开发的风险 人体临床试验；以及3)为RT-002过渡到 通过与合同研究组织的现有合作伙伴关系进行临床测试，危重疾病和危重 稳定CHO细胞RT-002生产和GMP认证的试验专家，组织和规划 IND前咨询FDA和设计所需的来自目标1和目标2的关键参数 I/IIa期临床试验。 AIMS的成功完成将使IND-Enabling研究、IND填报和初始阶段取得快速进展 一种新疗法的临床试验，用于治疗生命的重要和大部分未得到满足的临床需求- 威胁到流感的疾病。

Abstract Respana Therapeutics is advancing a proprietary first-in-class therapeutic monoclonal antibody (mAb), RT- 002, for the treatment of debilitating and often lethal inflammatory complications associated with acute respiratory conditions. We have identified a lead candidate, RT-002, and an equally promising alternative. RT-002 targets the surfactant protein A receptor SP-R210, a host-mediated target that holds the promise of efficacy regardless of pathogen evolution. Rigorous in vivo mouse studies have demonstrated not only reduction in mortality but restoration of lung health as well. Furthermore, RT-002 does not target an individual cytokine pathway, which can have negative effects. RT-002 thus has the potential to fill a significant gap in the therapeutics arsenal for influenza since the most widely used tools are vaccines to prevent infection and antiviral drugs to stop infection; however, these are limited by partial efficacy, vaccine hesitancy, and emergence of drug resistance. The objective of this Phase II proposal is to continue development of RT-002 and the backup with the goal of advancing the therapeutic toward clinical trials as quickly and efficiently as possible. Specifically, the Aims include: 1) Determine RT-002 pharmacological action in human blood through our functional immunophenotype assays to discern RT-002 target engagement and immune activation in human blood that will inform therapeutic design in alleviating aberrant immune activation in critically ill patients; 2) Establish pharmacological activity of RT-002 treatment for severe influenza utilizing humanized FcRn mice to establish safety, toxicity, pharmacodynamics, dosage, schedule, and duration of treatment to de-risk the development of RT-002 towards clinical trials in humans; and 3) Establish foundations for Phase I/IIa clinical trials for transition of RT-002 to clinical testing through existing partnerships with contractual research organizations, critical illness, and critical trials experts for production and GMP certification of RT-002 in stable CHO cells, and organization and planning of critical parameters from Aims 1 and 2 that are needed for pre-IND consultation with the FDA and the design of phase I/IIa clinical trials. Successful completion of the Aims will allow rapid progress toward IND-enabling studies, IND filling and initial clinical trials of a new therapeutic for an important and largely unmet clinical need for the treatment of life- threatening influenza illness.