Novel Small Molecule Drug Candidate for the Prevention of Bronchopulmonary Dysplasia

预防支气管肺发育不良的新型小分子候选药物

• 批准号: 10698418
• 负责人: Michaela Christina Kollisch-Singule
• 金额: $ 37.68万
• 依托单位: CMTX BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-03 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698418
• 关键词: AIDS with Kaposi' s sarcoma; Acne; Acute Lung Injury; Acute Respiratory Distress Syndrome; Affect; Agreement; Animal Model; Antibiotics; Asthma; Authorization documentation; Biotechnology; Bronchodilator Agents; Bronchopulmonary Dysplasia; Chemicals; Chest wall structure; Chronic lung disease; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Control Groups; Deformity; Disease; Disease Progression; Disease model; Disparate; Disseminated Malignant Neoplasm; Diuretics; Extremely low gestational age newborn; FDA approved; Family suidae; Formulation; Glioma; Goals; Good Manufacturing Process; Histopathology; Hospital Costs; Hydrocortisone; Infant; Inflammasome; Inflammation; Inflammatory; Injury; Intensive Care; International; Intervention; Intravenous; Intubation; Investigational Drugs; Investigational New Drug Application; Knowledge; Lead; Licensing; Lung; Marketing; Matrix Metalloproteinases; Measures; Mechanics; Mediating; Medical; Molecular; Morbidity - disease rate; Mothers; Mus; National Cancer Institute; Neonatal; Outcome; Oxygen; Pathogenesis; Pathologic; Pathway interactions; Periodontitis; Pharmaceutical Cares; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase Ib/II Clinical Trial; Predisposition; Pregnancy; Premature Birth; Premature Infant; Prevention; Prevention trial; Public Health; Publishing; Pulmonary Hypertension; Rattus; Recurrence; Refractory; Research; Respiratory Tract Infections; Respiratory distress; Risk; Rosacea; Safety; Sheep; Small Business Technology Transfer Research; Solid; Steroids; Structure of parenchyma of lung; Tetracyclines; Toxicology; United States; Very Low Birth Weight Infant; Work; adverse outcome; antenatal; authority; chronic respiratory disease; combat; commercial application; commercialization; design; drug candidate; drug development; effective intervention; efficacy study; extreme prematurity; forging; good laboratory practice; hemodynamics; hospital readmission; improved; long-term sequelae; lung injury; manufacture; manufacturing scale-up; mortality; novel; porcine model; pre-Investigational New Drug meeting; preclinical efficacy; prevent; respiratory; respiratory distress syndrome; secondary outcome; small molecule; standard of care; surfactant; systemic inflammatory response; therapeutically effective; treatment group; ventilation

PROJECT SUMMARY/ABSTRACT CMTx Biotech is a drug development company working to commercialize a proprietary, clinical-stage, small- molecule drug candidate for the prevention of respiratory distress syndrome (RDS) and its long-term sequelae, bronchopulmonary dysplasia (BPD), in preterm infants. BPD is a chronic respiratory disease that occurs in preterm infants who develop RDS from a combination of lung immaturity, inflammation, and mechanical injury from ventilation. BPD is the most common adverse outcome of preterm delivery, affecting up to 75% of infants born before 28 weeks of gestation worldwide. Every year in the U.S., approximately 380,000 of these infants are born, of which 50,000 are extremely low gestational age newborns (ELGANs), 35% (18,000) of which develop BPD. The median cost of hospitalization associated with BPD during the first year in very low birth weight infants is $377,871 per infant, compared to $175,836 per infant without BPD. There are currently no FDA-approved drugs specifically for the prevention and treatment of BPD. The current standard of care is focused on minimizing lung damage and providing respiratory support with the use of bronchodilators, diuretics, antibiotics, surfactant, and steroids, including antenatal steroid treatment of the mother before preterm birth. Most agents that are prescribed to prevent BPD are also used for the management of established BPD, and these therapies lack solid evidence of efficacy. A recent clinical study concluded that hydrocortisone is not effective at preventing BPD in premature infants or improving their survival. There remains a critical unmet need for safe and effective therapeutics for the prevention of BPD. Our lead drug candidate is a pleiotropic matrix metalloproteinase (MMP) modulator which inhibits pathologically- excessive collagenolysis and resolves systemic inflammation. Safety of the compound has already been demonstrated in Investigational New Drug (IND)-enabling studies. The drug has been evaluated in a number of clinical trials for the treatment of diseases as disparate as AIDS-related Kaposi’s sarcoma, recurrent high- grade gliomas, refractory metastatic cancer, acne, rosacea and periodontitis. The Specific Aims of this STTR are to determine the ability of our lead drug candidate to prevent the onset of BPD in a preterm piglet model, and to evaluate its effect on the pathogenesis of BPD and inflammatory pathways. Our long-term goal is to obtain approval from the FDA and comparable international regulatory authorities to market our drug candidate as a safe and effective intervention. We anticipate that our drug candidate will inhibit BPD progression, mitigate acute lung injury and respiratory distress, reduce the need for intensive care and intubation, and improve clinical outcomes for pre-term infants, including overall survival. Successful completion of these studies will allow CMTx Biotech to advance our lead drug candidate towards clinical trials for the prevention of BPD.

项目摘要/摘要 CMTX Biotech是一家药物开发公司，致力于商业化专有的临床阶段，小型 - 预防呼吸窘迫综合征（RD）及其长期后遗症的分子药物候选药物 早产儿的支气管肺发育不良（BPD）。 BPD是一种慢性呼吸道疾病，发生在 从肺不成熟，感染和机械损伤的组合发展RD的早产婴儿 从通风。 BPD是早产的最常见不利结果，影响多达75％的婴儿 出生于全球28周之前。每年在美国，大约有380,000个婴儿 诞生了，其中50,000个是极低的胎龄新生儿（Elgans），其中35％（18,000） 开发BPD。与BPD相关的住院费用中位数在非常低的出生中 体重婴儿的体重为每位婴儿377,871美元，而没有BPD的婴儿为175,836美元。目前没有 FDA批准的药物专门用于预防和治疗BPD。当前的护理标准是 专注于最大程度地减少肺损伤并通过使用支气管扩张剂提供呼吸道支持， 利尿剂，抗生素，表面活性剂和类固醇，包括母亲的抗肿类固醇治疗 早产。大多数用于防止BPD的代理商也用于管理 建立的BPD，这些疗法缺乏效率的可靠证据。最近的一项临床研究得出的结论是 氢化可的松无效预防早产儿或改善其存活率的BPD。那里 对于预防BPD的安全有效疗法仍然是至关重要的未满足的需求。我们的领导 候选药物是多效基质金属蛋白酶（MMP）调节剂，它抑制病理学 过度的胶原分解并解决了全身感染。大院的安全已经存在 在研究新药（IND）的研究中证明。该药物已在多个 治疗与艾滋病相关的卡波西肉瘤等疾病治疗的临床试验 等级神经胶质瘤，难治性转移性癌，痤疮，酒渣鼻和牙周炎。此sttr的具体目的 是确定我们的铅药物候选者在早产小猪模型中预防BPD发作的能力， 并评估其对BPD和炎症途径的发病机理的影响。我们的长期目标是 获得FDA和可比的国际监管机构的批准，以推销我们的候选药物 作为安全有效的干预。我们预计我们的候选药物将抑制BPD的进展，减轻 急性肺损伤和呼吸窘迫，减少重症监护和插管的需求，并改善 前婴儿的临床结果，包括总体生存。这些研究的成功完成将 允许CMTX Biotech将我们的主要药物候选者推向预防BPD的临床试验。