Late preclinical development of a treatment for acute inflammatory disease derived from M.tuberculosis bacteria

全世界约有20亿人感染结核细菌（mTB）；它们已经进化了几千年，通过产生调节宿主免疫系统的蛋白质，隐藏在体内。这些蛋白质已被证明与身体的自然炎症过程相互作用并减少。Peptinnovate的创新Peptinnovate的方法是解锁这些蛋白质的抗炎活性，并开发治疗急性器官衰竭和慢性阻塞性肺病等衰弱性疾病的新药。基于进化、大自然的创造力和Peptinnovate的药物发现和开发技能，我们已经将这些蛋白质修饰成更像药物的分子，并正在将候选分子PIN201104推向临床。根据MHRA的科学建议和批准以及之前的SMART支持（720364），该项目将使我们的候选药物PIN201104能够在GLP非临床毒理学研究中进行评估，并按照GMP标准生产和配制，通过静脉给药急性使用。除此之外，我们还将在一系列炎症疾病模型中开展进一步的体内疗效研究，以扩大该分子的治疗效用。•根据gmp标准生产和评估PIN201104原料药和制剂，为临床研究做好准备；•在一系列动物炎症模型中证明其有效性，以扩大PIN201104的临床适应症范围。益处、结果和影响炎性疾病治疗的全球市场是巨大的（700亿美元），然而最近的安全恐慌被归因于一些关键药物。Peptinnovate在潜在治疗选择方面的模式转变将对数百万患者的生活产生深远的影响，减轻医疗保健提供者的负担，并帮助建立可持续发展的英国制药公司。

Tuberculosis bacteria (mTB) are present in about 2 billion people worldwide; they haveevolved over millennia to remain hidden in the body by producing proteins that modulate thehost's immune system. These proteins have been shown to interact with and reduce the body'snatural inflammatory processes.Peptinnovate’s innovationPeptinnovate’s approach is to unlock the anti-inflammatory activity of these proteins and todevelop new medicines for debilitating diseases such as acute organ failure and COPD.Building on evolution, nature's ingenuity and employing Peptinnovate’s drug discovery anddevelopment skills we have modified these proteins to more drug-like molecules and areprogressing the candidate molecule, PIN201104, to the clinic.AimsFollowing scientific advice and approval from the MHRA and previous SMART support(720364), this project will enable our drug candidate, PIN201104, to be evaluated in GLP nonclinicaltoxicology studies, and manufactured and formulated to GMP standards for acute usevia intravenous dosing. Alongside this we will also carry out further in vivo efficacy studies ina range of inflammatory disease models to widen the therapeutic utility of the molecule.Objectives• To perform MHRA approved GLP toxicology and safety pharmacology studies in therat and dog,• To manufacture and evaluate PIN201104 drug substance and drug product to GMPstandards ready for clinical studies,• To demonstrate efficacy in a range of animal models of inflammation to extendPIN201104’s range of clinical indications.Benefits, outcomes and impactsThe worldwide market for inflammatory disease treatment is substantial (>$70 billion),however recent safety scares have been attributed to a number of key drugs. Peptinnovate’sparadigm shift in potential treatment options will have a profound impact on the lives ofmillions of patients, reducing the burden on the healthcare providers and helping to build asustainable, UK based pharmaceutical company.