Novel Small Molecule Drug Candidate for the Prevention of Bronchopulmonary Dysplasia

项目总结/摘要 CMTx Biotech是一家药物开发公司，致力于将一种专有的、临床阶段的、小型的、 预防呼吸窘迫综合征（RDS）及其长期后遗症的分子候选药物， 支气管肺发育不良（BPD），早产儿。BPD是一种慢性呼吸道疾病， 由于肺不成熟、炎症和机械损伤的组合而发展为RDS的早产儿 从通风。BPD是早产最常见的不良结局，影响高达75%的婴儿 全世界怀孕28周前出生的婴儿。每年在美国，大约有38万婴儿 其中50，000名是极低胎龄新生儿（ELGAN），其中35%（18，000名） 开发BPD。极低出生婴儿第一年内与BPD相关的住院费用中位数 体重的婴儿是每名婴儿377，871美元，而没有BPD的婴儿是每名婴儿175，836美元。目前没有 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 集中于最小化肺损伤和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，包括产前类固醇治疗的母亲之前， 早产大多数用于预防BPD的药物也用于治疗 这些治疗缺乏有效性的可靠证据。最近的一项临床研究得出结论， 氢化可的松不能有效预防早产儿的BPD或改善其存活率。那里 仍然是对预防BPD的安全有效的治疗剂的关键的未满足的需求。我们的首席 候选药物是一种多效性基质金属蛋白酶（MMP）调节剂， 过度的胶原蛋白溶解和解决全身性炎症。基地的安全性已经 在新药临床试验（IND）启动研究中得到证实。该药物已在多个 治疗艾滋病相关的卡波西肉瘤等不同疾病的临床试验， 恶性胶质瘤、难治性转移癌、痤疮、酒渣鼻和牙周炎。本STTR的具体目标 是为了确定我们的先导候选药物在早产仔猪模型中预防BPD发作的能力， 并评价其对BPD发病机制及炎症通路的影响。我们的长期目标是 获得FDA和类似国际监管机构的批准，以销售我们的候选药物 安全有效的干预措施我们预计，我们的候选药物将抑制BPD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要，并改善 早产儿的临床结局，包括总生存率。成功完成这些研究将 允许CMTx Biotech将我们的主要候选药物推向预防BPD的临床试验。

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.