Developing Intravesical Liposomes for Interstitial Cystitis

描述(申请人提供)：LP08是一种治疗间质性膀胱炎(IC)的新型膀胱内疗法，IC是一种病因不明的慢性疾病，人们对其知之甚少，包括刺激性膀胱症状和严重影响生活质量的盆腔疼痛。在IC/PBS中，一般认为有两种不同的亚型。溃疡性(经典)IC和非溃疡性IC/PBS在膀胱镜检查结果和对治疗的症状反应方面明显不同。LP08是一种受专利保护的IC研究药物，由纯脂质体组成。已知LP08的纯化磷脂成分在作为静脉营养成分食用或输送时作为食物来源是安全的。人们不指望一种新的膀胱给药途径会带来任何安全问题。我们将在溃疡性IC患者的IND试验中研究LP08的安全性和有效性。利培拉制药公司是由LP08的发明者于2005年5月成立的公司。Lipella已经获得了一期和二期SBIR支持，以及来自生物技术投资组织匹兹堡生命科学温室组织和经认可的投资者的大量资金支持。IND临床试验将在威廉·博蒙特医院进行，威廉·博蒙特医院是这项STTR的共同申请者。博蒙特公司泌尿科主任肯尼斯·彼得斯是国际公认的溃疡性IC治疗和研究领域的领导者，拥有100多名溃疡性IC患者的数据库。在过去的15年里，威廉·博蒙特医院的泌尿科一直是世界领先的IC研究中心之一，也是NIDDK赞助的包括ICDB、ICCTG和ICCRN在内的多机构IC试验的顶级中心。这项快速通道科技创新研究提案推进了由已完成的前一阶段NIH SBIR赠款以及随后的第二阶段SBIR赠款资助的商业研究，该赠款也已获得资金，目前正在进行中。(之所以选择快速通道应用程序，是因为在第一阶段生产的试点人类批次可以产生IND应用所需的监管数据，并作为初始临床供应，而不需要考虑产品的保质期和储存。)这些先前和现有的赠款用于临床前开发一种治疗IC的新方法。目前的STTR提案将为该产品的临床开发提供资金。这项STTR的成功完成将为一种具有大量未得到满足的临床需求的综合症的新疗法提供重要的临床数据，这是一项对机构投资者具有极大吸引力的资产。总之，这项建议的目的是通过利用Lipella制药公司cGMP脂质体制造能力和William Beaumont医院集成电路专用临床能力的持续结果，为实验性间质性膀胱炎药物获得重要的临床数据。公共卫生相关性：成功完成这项STTR将为间质性膀胱炎的新疗法提供重要的临床数据，间质性膀胱炎是一种具有大量未满足临床需求的综合征。开发IND以及生产第一批供人使用的产品是目前STTR提案第一阶段部分的重点。FDA对IND的批准是这项快速通道提案第一阶段和第二阶段之间的里程碑。IND临床试验的制造和操作是这项STTR赠款提案第二阶段部分的重点。

DESCRIPTION (provided by applicant): LP08 is a novel intravesical treatment for interstitial cystitis (IC), a poorly understood chronic disorder of unknown etiology consisting of irritative bladder symptoms and pelvic pain that dramatically affects quality of life. In IC/PBS, two distinct subtypes are generally recognized. Ulcerative (classic) IC and non-ulcerative IC/PBS clearly differ in terms of cystoscopic findings and symptom response to treatments. LP08 is a patent-protected investigational drug for IC comprised of pure liposomes. The purified phospholipid component of LP08 is known to be safe as a food source when eaten or delivered as a component of intravenous nutrition. There is no expectation that a novel route of bladder administration will present any safety issues. We will investigate the safety and efficacy of LP08 in an IND trial of ulcerative IC patients. Lipella Pharmaceuticals Inc. is a company formed by the inventors of LP08 in May of 2005. Lipella has received phase-I and phase-II SBIR support, as well as significant financial support from the Pittsburgh Life Sciences Greenhouse, a biotechnology investment organization, and accredited investors. The IND clinical trial will be conducted at the William Beaumont Hospital, the co-applicant of this STTR. Beaumont's urology department chairman, Kenneth Peters, is internationally recognized as a leader in the treatment and study of ulcerative IC and has a database of over 100 ulcerative IC patients. The urology department at the William Beaumont Hospital has been one of the leading centers in the world for the past 15 years on the study of IC and a top center in the NIDDK sponsored multi-institutional trials on IC including the ICDB, ICCTG and the ICCRN. This Fast-track STTR proposal advances commercial research funded by a prior phase-I NIH SBIR grant which has been completed, as well as a subsequent phase-II SBIR grant which has also been funded and is currently in progress. (The reason that the fast-track application process is chosen is so the pilot human batch produced in phase-I can produce both the regulatory data needed for the IND application and serve as the initial clinical supply without concerns for product shelf life and storage.) These prior and existing grants fund the preclinical development of a novel treatment for IC. The current STTR proposal would fund the clinical development of this product. Successful completion of this STTR would provide significant clinical data on a novel therapy for a syndrome with large unmet clinical demand, an asset highly attractive to institutional investors. In Summary, the aims of this proposal are designed to obtain significant clinical data for an experimental interstitial cystitis drug, by leveraging ongoing results of the cGMP liposome manufacturing capabilities at Lipella Pharmaceuticals and the IC-specific clinical capabilities of William Beaumont Hospital. PUBLIC HEALTH RELEVANCE: Successful completion of this STTR would provide significant clinical data on a novel therapy for interstitial cystitis, a syndrome with large unmet clinical demand. The development of an IND as well as the production of the first batch of product for human use is the focus of the phase-I portion of the current STTR proposal. IND approval from the FDA is the milestone between the phase-I and phase-II portions of this fast-track proposal. Manufacturing for and operational of the IND clinical trial is the focus of the phase-II portion of this STTR grant proposal.