Pre-clinical validation of a potent candidate in the fight against AMR HCAI

对抗 AMR HCAI 的有效候选药物的临床前验证

• 批准号: 971631
• 金额: $ 150.62万
• 依托单位: AMPROLOGIX LIMITED
• 依托单位国家: 英国
• 项目类别: Small Business Research Initiative
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=971631
• 关键词: Pre; clinical; validation; potent; candidate

Antimicrobial resistant (AMR) bacteria kill over 25,000 people a year in Europe and resistance rates are climbing rapidly worldwide. There is a critical need for novel classes of antibiotics to tackle the rise of antibiotic resistant bacteria and serve as scaffolds for derivatisation, diversification and enhancement of efficacy, a strategy proven successful with previous generations of drugs such as penicillin. Amprologix Ltd is using machine learning, bioinformatic peptide design strategies and high-throughput biological assays to develop an exciting new class of antimicrobial biologics (ABs) focused around a family called epidermicins. These ABs have no known resistance liabilities and rapidly kill bacteria at very low doses. Amprologix is currently developing narrow-spectrum epidermicins that are specifically active against either Gram positive or Gram-negative AMR pathogens. In recent work, Amprologix has shown unique benefits of epidermicin NI01, our lead compound, over current gold-standard therapy (mupirocin: Bactroban) in a key animal infection model for MRSA; a single dose of NI01 was as effective as six doses of mupirocin. This level of efficacy, combined with the broader properties of epidermicin NI01 mean it has excellent potential for use as a topical therapy for prevention and treatment of infections caused by bacteria like Staphylococcus aureus and MRSA, which are leading causes of skin and soft tissue infections in Europe. MRSA is also one of the leading causes of healthcare associated infections (HCAI) in the UK and Europe and has been designated as a high priority target pathogen. In both hospital and community settings, the rate of infections caused by MRSA and S. aureus are increasing and resistance to front-line therapies is growing. Consequently, there is an urgent need for new agents to prevent and treat infection caused by these organisms. In this SBRI-funded project, Amprologix will fast-track the pre-clinical development of NI01, the first anti-MRSA/S. aureus epidermicin. We will optimise the formulation of epidermicin and demonstrate its safety in a pre-clinical evaluation of toxicity in a topical application. Building on our previous successes in developing a high-yield manufacturing process for epidermicin antibiotics in a commercially-scalable yeast production system, we will deliver a GMP compliant pre-master cell bank, ready for manufacture of clinical grade epidermicin. Success in this project will allow rapid progression to a phase-1 human clinical trial investigating the topical application of the antibiotic to prevent MRSA infections. If successful, this will de-risk NI01 for human use and allow Amprologix to raise sufficient venture capital to bring its lead compound to market and fund the development of other 'narrow spectrum' epidermicins from the same class of antibiotics. Ultimately this will bring a powerful new platform of highly effective and adaptable antibiotic drugs to market, greatly benefiting the NHS and other healthcare systems worldwide.

在欧洲，耐药性（AMR）细菌每年导致25，000多人死亡，全球范围内的耐药率正在迅速攀升。迫切需要新型抗生素来应对抗生素耐药性细菌的增加，并作为衍生化，多样化和增强功效的支架，这是前几代药物（如青霉素）证明成功的策略。Amprologix Ltd正在使用机器学习，生物信息学肽设计策略和高通量生物测定来开发一种令人兴奋的新型抗菌生物制剂（AB），重点关注一个名为epidermicins的家族。这些AB没有已知的耐药性，并在非常低的剂量下迅速杀死细菌。Amprologix目前正在开发对革兰氏阳性或革兰氏阴性AMR病原体具有特异性活性的窄谱表皮霉素。在最近的工作中，Amprologix在MRSA的关键动物感染模型中显示了我们的先导化合物表皮霉素NI 01相对于当前金标准疗法（莫匹罗星：百多邦）的独特益处;单剂量NI 01与六剂量莫匹罗星一样有效。这种疗效水平，加上表皮霉素NI 01的更广泛特性，意味着它具有很好的潜力，可用作预防和治疗由金黄色葡萄球菌和MRSA等细菌引起的感染的局部治疗，这些细菌是欧洲皮肤和软组织感染的主要原因。MRSA也是英国和欧洲医疗保健相关感染（HCAI）的主要原因之一，并已被指定为高优先级目标病原体。在医院和社区环境中，MRSA和S。金黄色葡萄球菌正在增加，对一线治疗的耐药性也在增加。因此，迫切需要新的药剂来预防和治疗由这些生物体引起的感染。在这个SBRI资助的项目中，Amprologix将快速跟踪NI 01的临床前开发，NI 01是第一个抗MRSA/S的药物。金黄色表皮菌素我们将优化表皮霉素的配方，并在局部应用的临床前毒性评价中证明其安全性。基于我们之前在商业化可扩展的酵母生产系统中开发表皮霉素抗生素高产生产工艺的成功经验，我们将提供符合GMP要求的预主细胞库，为生产临床级表皮霉素做好准备。该项目的成功将允许快速进展到1期人体临床试验，研究局部应用抗生素预防MRSA感染。如果成功，这将降低NI 01用于人类的风险，并允许Amprologix筹集足够的风险资本，将其先导化合物推向市场，并资助开发来自同类抗生素的其他“窄谱”表皮素。最终，这将为市场带来一个强大的高效和适应性强的抗生素药物新平台，极大地受益于NHS和全球其他医疗保健系统。