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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目概要/摘要 CMTx Biotech 是一家药物开发公司，致力于将专有的、临床阶段的、小型的用于预防呼吸窘迫综合征（RDS）及其长期后遗症的候选分子药物，早产儿支气管肺发育不良 (BPD) 是一种发生于早产儿的慢性呼吸道疾病。由于肺部不成熟、炎症和机械损伤而导致 RDS 的早产儿通气引起的 BPD 是早产最常见的不良后果，影响高达 75% 的婴儿。在美国，全世界每年约有 380,000 名妊娠 28 周前出生的婴儿。出生，其中 50,000 名极低胎龄新生儿 (ELGAN)，其中 35% (18,000) 极低出生人口第一年与 BPD 相关的住院费用中位数。每个婴儿体重为 377,871 美元，而没有 BPD 的婴儿为 175,836 美元。 FDA 批准的专门用于预防和治疗 BPD 的药物目前的护理标准是。专注于最大限度地减少肺部损伤并使用支气管扩张剂提供呼吸支持，利尿剂、抗生素、表面活性剂和类固醇，包括母亲产前的类固醇治疗大多数用于预防 BPD 的药物也可用于治疗早产。最近的一项临床研究得出的结论是，这些疗法缺乏确凿的疗效证据。氢化可的松不能有效预防早产儿 BPD 或提高其生存率。对于预防 BPD 的安全有效的治疗方法仍然是一个未得到满足的重要需求。候选药物是一种多效性基质金属蛋白酶（MMP）调节剂，可抑制病理性- 过度胶原溶解并解决全身炎症，该化合物的安全性已得到证实。该药物已在多项研究性新药（IND）研究中得到证实。治疗不同疾病的临床试验，如与艾滋病相关的卡波西肉瘤、复发性高级神经胶质瘤、难治性转移癌、痤疮、红斑痤疮和牙周炎。目的是确定我们的主要候选药物预防早产仔猪模型中 BPD 发作的能力，并评估其对 BPD 发病机制和炎症途径的影响。获得 FDA 和类似国际监管机构的批准来营销我们的候选药物作为一种安全有效的干预措施，我们预计我们的候选药物将抑制 BPD 的进展，缓解症状。急性肺损伤和呼吸窘迫，减少重症监护和插管的需要，并改善早产儿的临床结果，包括成功完成这些研究将。让 CMTx Biotech 能够将我们的主要候选药物推进到预防 BPD 的临床试验中。