Strain-Independent Therapeutic Antibodies for Influenza

流感病毒毒株无关的治疗性抗体

基本信息

批准号：
10338076
负责人：
Lawrence Michael Kauvar
金额：
$ 99.98万
依托单位：
TRELLIS BIOSCIENCE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10338076
关键词：
Address Advanced Development Aerosols Affinity Agreement Amantadine Antibiotic Resistance Antibody-Dependent Enhancement Antiviral Agents Award Bacterial Proteins Binding Biological Assay Biological Sciences Birds Buffers Cardiotoxicity Cities Clinical Communicable Diseases Cytomegalovirus Development Disease Dose Drug Industry Drug Kinetics Drug resistance Formulation Funding Grant Guidelines Human Human Cloning In Vitro Industry Infection Inflammatory Influenza Influenza A Virus, H7N9 Subtype Influenza A virus Influenza B Virus Influenza Hemagglutinin Influenza Therapeutic Inhalation Legal patent Licensing Malignant Neoplasms Microbial Biofilms Monoclonal Antibodies Mus Nebulizer Neuraminidase inhibitor Oseltamivir Patients Pharmaceutical Preparations Pharmacologic Substance Phase Phase I Clinical Trials Phase II Clinical Trials Polymerase Predisposition Privatization Production Property Proteins Rattus Resistance Respiratory System Respiratory syncytial virus Safety Serum Small Business Innovation Research Grant Technology Testing Therapeutic antibodies Toxic effect Toxicology Vaccines Ventilator Virus Work antibody test biosafety level 3 facility cell bank clinical development cohort comparative efficacy efficacy study expectation experience flu activity follow-up high risk human monoclonal antibodies human tissue improved improved outcome in vivo influenza virus strain influenzavirus inhibitor innovation mouse model neutralizing antibody nonhuman primate pandemic disease phase III trial physical property preclinical development programs resistant strain response small molecule small molecule therapeutics symposium

项目摘要

SUMMARY In this Phase IIB proposal, we seek funding to complete the IND-enabling development of CF-404, a mixture of three native human monoclonal antibodies (mAbs). Activity has been established in mouse models against representatives of all major circulating strains of influenza A and B. By providing a pan-influenza treatment, we avoid delays associated with strain typing, with improved outcomes expected from the prompt treatment. We specifically propose here to address regulatory issues relating to delivery of the mAb mixture by inhalation. Our background work demonstrated that inhaled delivery provides superior efficacy compared to systemic delivery, at ~10-fold lower dose. The inhalation technology from industry leader Aerogen Pharma is established as suitable for hospitalized patients, including those on a ventilator. Due to drug resistance to the existing influenza therapeutic drugs, there is a high need for our product. The first class of small molecule therapeutics, the amantadines, are now largely useless due to drug resistance. The second class, neuraminidase inhibitors, are currently experiencing similar emergence of resistance. The newest class, polymerase inhibitors, has already shown worrisome signs of early emergence of drug resistant strains (10% in the Phase 3 trials). By contrast, intensive selection in vitro for virus that escapes our mAbs has shown that resistance is likely to be far less common than for the small molecule antivirals. The impact of CF-404 is thus expected to be high.

概括在此阶段IIB提案中，我们寻求资金来完成CF-404的成熟开发，这是三种本地人类单克隆抗体（mAb）。在鼠标模型中已经建立了活动流感和B的所有主要循环菌株的代表。避免与应变分型相关的延迟，并通过迅速治疗预期的结果得到改善。我们在这里特别提议解决与通过吸入递送MAB混合物有关的调节问题。我们的背景工作表明，与全身交付相比，吸入的输送提供了较高的功效下剂量约10倍。从行业领导者Aerogen Pharma的吸入技术被确定为适用于住院的患者，包括呼吸机的患者。由于对现有流感的耐药性治疗药物，我们的产品非常需要。第一类小分子疗法，阿曼达丁（Amantadines）现在由于耐药性而在很大程度上毫无用处。第二类神经氨酸酶抑制剂是目前经历了类似的抵抗。最新类，聚合酶抑制剂已经显示出令人担忧的抗药性菌株早期出现的迹象（在第三阶段试验中为10％）。相比之下逃脱我们的mAb的病毒的体外选择，表明抗性可能少得多常见的是小分子抗病毒药。因此，CF-404的影响预计会很高。