The First LANCL2-based therapeutic for influenza

首个基于 LANCL2 的流感疗法

• 批准号: 10325782
• 负责人: Raquel Hontecillas
• 金额: $ 30万
• 依托单位: BIOTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-11 至 2022-12-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325782
• 关键词: 2019-nCoV; Address; Agonist; Antiviral Agents; Antiviral resistance; Binding; Biological Response Modifier Therapy; Biotechnology; COVID-19 pandemic; Cells; Cessation of life; Chemistry; Clinical; Clinical Trials; Communicable Diseases; Computer Models; Coupled; Data; Development; Disease; Dose; Drug resistance; Economics; Epidemic; Epithelial Cells; Funding; Goals; Histology; Hospital Costs; Human; Immune response; In Vitro; Infection; Inflammation; Influenza; Influenza A virus; Influenza Therapeutic; Interleukin-6; Intervention; Knockout Mice; Knowledge; Lead; Ligands; Ligase; Literature; Lung; Metabolic; Modeling; Molecular Target; Outcome; Pathogenesis; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Positioning Attribute; Precision Health; Public Health; Recovery; Regulatory Pathway; Risk; Role; Safety; Small Business Innovation Research Grant; Specificity; Symptoms; TNF gene; Technology; Testing; Therapeutic; Time; Treatment Efficacy; Vaccination; Vaccine Therapy; Vaccines; Variant; Viral; Viral Load result; Virus; Virus Diseases; Virus Replication; War; Weight; Work; base; chikungunya; commercial application; cytokine release syndrome; flu; global health; improved; influenza infection; influenza outbreak; influenzavirus; lanthionine; mortality; mouse model; novel; novel therapeutics; pandemic influenza; pathogen; pre-clinical; precision medicine; prevent; research and development; respiratory virus; response; safety assessment; scale up; seasonal influenza; success; synergism; targeted treatment; therapeutic target; tissue repair; universal vaccine; vaccine access

The First LANCL2-based therapeutic for influenza Biotherapeutics, Inc (BTI) is a clinical-stage biotech company that synergistically combines the power of advanced computational modeling with translational experimentation to accelerate the development of novel products for precision medicine and health. This Phase 1 SBIR application emerges from substantial preclinical data showing the potential of lanthionine synthetase C-like 2 (LANCL2) agonists as host-based therapeutics for viral diseases. Our Product: BT-63, a novel lead LANCL2 agonist ligand, selectively binds to LANCL2 and exerts promising therapeutic efficacy in mouse models of influenza A virus (IAV). In this Phase I we will focus on influenza virus to characterize the role of LANCL2 as therapeutic target with broad antiviral effects. Background: infectious diseases caused by emerging and re-emerging viruses are a significant public health challenge. Influenza remains a significant public health threat despite available antivirals and vaccines. The absence of effective universal vaccines and antivirals coupled with the rising rates of antiviral resistance justifies the need to develop novel host-based antivirals. BTI identified LANCL2 as a novel target during viral infections. LANCL2 agonistic drugs down-regulate viral entry and replication while protecting against the virus-induced cytokine storm, mortality, pathology and disease. The Specific Aims of this SBIR Phase 1 application are to: AIM 1. Validate LANCL2 as a new host target for treating influenza infections: we will to optimize dosing and therapeutic window and validate LANCL2 as the molecular target of BT-63. AIM 2: Evaluate the antiviral mechanisms and spectrum of BT-63: we will test the hypothesis that BT-63 exerts broad spectrum antiviral effect by modulating metabolic responses of the host cell. Mayor expected outcomes: BT-63 offers at least a 50% protection against mortality, suppresses by 10-fold the expression of proinflammatory markers IL-6 and TNFα, the mechanism is LANCL2-dependent, and BT-63 has broad antiviral spectrum against pH-dependent viruses. . SBIR Phase II will assess the potential for synergism with and comparison against current antivirals and vaccines, expand LANCL2 efficacy and antiviral knowledge into other viruses and advance lead derivatives along the FDA regulatory pathway through ADME-Tox and safety assessments with a key milestone of submitting an IND application within 1 year of funding. Commercial Application: Technology generated by this R&D project could disrupt a $50B annual market.

首个基于LANCL 2的流感治疗药物 Biotherapeutics，Inc（BTI）是一家临床阶段的生物技术公司，协同结合了 先进的计算建模与平移实验，以加速开发新的 精准医疗和健康产品。这一1期SBIR应用来自大量的临床前研究， 数据显示羊毛硫氨酸合成酶C样2（LANCL 2）激动剂作为基于宿主的治疗剂的潜力， 病毒性疾病 我们的产品：BT-63，一种新型的前导LANCL 2激动剂配体，选择性地结合LANCL 2，并发挥有前途的作用。 在甲型流感病毒（IAV）的小鼠模型中的治疗功效。在第一阶段，我们将重点关注流感病毒 以表征LANCL 2作为具有广泛抗病毒作用的治疗靶标的作用。 背景：由新出现和再出现的病毒引起的传染病是一个重大的公共卫生问题 挑战.尽管有抗病毒药物和疫苗，流感仍然是一个重大的公共卫生威胁。的 缺乏有效的通用疫苗和抗病毒药物，加上抗病毒药物耐药性的上升， 开发新型宿主抗病毒药物的必要性。BTI将LANCL 2确定为病毒感染期间的新靶标。 LANCL 2激动剂药物下调病毒进入和复制，同时保护免受病毒诱导的细胞凋亡。 细胞因子风暴、死亡率、病理学和疾病。 SBIR第1阶段应用的具体目标是： AIM 1. HLANCL 2作为治疗流感感染的新宿主靶点：我们将优化剂量 和治疗窗，并验证LANCL 2作为BT-63的分子靶点。 目的2：评价BT-63的抗病毒机制和抗病毒谱：我们将检验BT-63 通过调节宿主细胞的代谢反应发挥广谱抗病毒作用。 市长预期的结果：BT-63提供至少50%的保护，防止死亡，抑制10倍， 促炎标志物IL-6和TNFα的表达，其机制是LANCL 2依赖性的，BT-63具有 对pH依赖性病毒的广谱抗病毒谱。 . SBIR第二阶段将评估与当前抗病毒药物的协同作用和比较潜力， 疫苗，扩大LANCL 2的功效和抗病毒知识到其他病毒和先进的铅衍生物沿着 通过ADME-Tox和安全性评估的FDA监管途径，其中一个关键里程碑是提交 IND申请在一年内获得资助。 商业应用：该研发项目产生的技术可能会扰乱每年500亿美元的市场。