Treatment of Inflammatory Complications of Respiratory Infection

呼吸道感染炎症并发症的治疗

• 批准号: 10756583
• 负责人: Timothy J Pelura
• 金额: $ 100万
• 依托单位: RESPANA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-20 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10756583
• 关键词: Acceleration; Acute; Address; Adult; Alveolar Macrophages; Animal Model; Antibodies; Antiviral Agents; Applications Grants; Asthma; Biochemical; Biological Assay; Blood; Body Weight; Certification; Cessation of life; Childhood; Chinese Hamster Ovary Cell; Chronic; Clinical; Clinical Trials; Critical Illness; Development; Drug Kinetics; Drug resistance; Economics; Evolution; Fibrosis; Foundations; Goals; Hospitalization; Human; Hypoxia; Immunophenotyping; Impaired cognition; Individual; Infection; Infection prevention; Inflammation; Inflammatory; Influenza; Injectable; Intervention; Lead; Life; Lung; Measures; Mediating; Medical; Medical Care Costs; Monoclonal Antibodies; Morbidity - disease rate; Mus; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmacodynamics; Pharmacologic Actions; Phase; Preclinical Testing; Prevention; Production; Protein Isoforms; Public Health; Recovery; Reporting; Research; Resolution; Respiratory Tract Infections; Respiratory physiology; Risk; Safety; Schedule; Small Business Technology Transfer Research; Survivors; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Toxic effect; United States; Vaccines; Validation; Virus Diseases; Work; Writing; airway obstruction; biophysical properties; candidate selection; clinical candidate; clinically relevant; commercialization; cost estimate; cytokine; design; differential expression; disability; dosage; high risk; humanized mouse; immune activation; improved outcome; in vivo; influenza infection; innovation; interstitial; lead candidate; lung health; mortality; murine monoclonal antibody; neonatal Fc receptor; novel; novel therapeutics; pandemic disease; pandemic influenza; pathogen; pharmacologic; phase 1 designs; pre-Investigational New Drug meeting; preclinical efficacy; product development; prototype; research clinical testing; respiratory; response; restoration; seasonal influenza; standard of care; surfactant protein A receptor; therapeutic candidate; timeline; tool; treatment duration; trend; vaccine hesitancy

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.

摘要 Respana Therapeutics正在推进一种专有的一流治疗性单克隆抗体（mAb），RT- 002，用于治疗与急性呼吸道疾病相关的使人衰弱且通常致命的炎性并发症 条件我们已经确定了一个主要候选人，RT-002，和一个同样有前途的替代品。RT-002靶 表面活性剂蛋白A受体SP-R210，一种宿主介导的靶点， 病原体的进化 严格的小鼠体内研究表明，不仅死亡率降低，而且肺功能恢复 健康也是。此外，RT-002不靶向单个细胞因子途径，其可以具有以下特征： 负面影响因此，RT-002有可能填补流感治疗药物库中的重大空白 因为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， 这些都受到部分效力、疫苗犹豫和抗药性出现的限制。 第二阶段提案的目标是继续开发RT-002和备份，目标是 尽可能快速有效地将治疗方法推向临床试验。具体而言，目标 包括：1）通过我们的功能免疫表型测定RT-002在人体血液中的药理作用 用于辨别人血液中RT-002靶标接合和免疫活化的测定， 设计，以减轻危重患者的异常免疫激活; 2）确定 RT-002利用人源化FcRn小鼠治疗严重流感以确定安全性、毒性 药效学、剂量、时间表和治疗持续时间，以降低RT-002发展为 3）为RT-002向临床试验过渡的I/IIa期临床试验奠定基础。 通过与合同研究组织、危重病和危重病的现有合作伙伴关系进行临床试验 RT-002在稳定CHO细胞中的生产和GMP认证的试验专家，以及组织和规划 目的1和2中与FDA进行IND前咨询所需的关键参数和设计 I/IIa期临床试验。 目标的成功完成将使IND使能研究、IND填写和初始 一种新的治疗方法的临床试验，用于治疗生命的重要且基本上未满足的临床需求， 威胁流感疾病。