Novel Small Molecule Drug Candidate for the Prevention of Bronchopulmonary Dysplasia

项目摘要/摘要 CMTx Biotech是一家药物开发公司，致力于将一种专利的、临床阶段的、小型的. 预防呼吸窘迫综合征(RDS)及其长期后遗症的候选分子药物， 早产儿支气管肺发育不良(BPD)。BPD是一种慢性呼吸道疾病，发生于 因肺不成熟、炎症和机械损伤而发展为RDS的早产儿 从通风系统。BPD是早产最常见的不良后果，影响高达75%的婴儿 在世界各地出生在怀孕28周之前。在美国，每年大约有38万名这样的婴儿 出生，其中50,000人是极低胎龄儿(Elgans)，其中35%(18,000人) 发展BPD。极低出生人口第一年内与BPD相关的住院费用的中位数 婴儿体重为每个婴儿377,871美元，而没有BPD的每个婴儿为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 重点是通过使用支气管扩张剂来最大限度地减少肺损伤和提供呼吸支持， 利尿剂、抗生素、表面活性物质和类固醇，包括产前给予母亲的类固醇治疗 早产。大多数用于预防BPD的处方药也用于管理 已经建立了BPD，而这些疗法缺乏疗效的确凿证据。最近的一项临床研究得出结论， 氢化可的松在预防早产儿BPD或提高他们的存活率方面无效。那里 对于预防BPD的安全和有效的疗法，仍然是一个严重的未得到满足的需求。我们的领先优势 候选药物是一种多效性基质金属蛋白酶(MMP)调节剂，它从病理上抑制- 过度的胶原酶分解和消除全身炎症。大院的安全已经被 在研究性新药(IND)使能研究中得到证实。这种药物已经在许多方面进行了评估 治疗各种疾病的临床试验，如艾滋病相关的卡波西肉瘤，复发率高的 分级胶质瘤、难治性转移癌、痤疮、酒渣鼻和牙周炎。这项技术援助计划的具体目标 是为了确定我们的候选先导药物在早产仔猪模型中预防BPD发病的能力， 并评价其在BPD发病机制及炎症途径中的作用。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 作为一种安全有效的干预手段。我们预计我们的候选药物将抑制BPD的进展，缓解 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，包括总存活率。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.