Novel antifungal discovery from mining unexplored microbes

每年有超过1.5亿人受到严重真菌疾病的影响，全球有170万人死亡。最严重的感染包括侵袭性曲霉病(IA)：一种与医疗保健相关的主要感染，死亡率高达95%。目前IA的治疗方案仅限于三种药物类别，疗效低，不良反应严重，治疗负担高。这些感染的治疗周期平均花费90K GB的医疗费用。由于过去20年没有新的抗真菌药物进入市场，因此迫切需要新的抗真菌治疗方案来对抗曲霉感染，并面临着开发更广泛的抗真菌感染新解决方案的重大市场机遇。临床使用的抗真菌药物类别中有三分之二来自实验室容易培养的~1%的微生物。这种生物资源现在已经被新型抗真菌药物耗尽，发现新的合成解决方案的努力未能填补这一空白。访问剩余99%的未培养微生物是发现新抗真菌药物的最佳机会。BactoBio开发了一个结合合成生物学、下一代测序和机器学习的平台来培养以前无法培养的微生物。到目前为止，我们已经独家获得了1500种新的和未开发的微生物物种。在这个项目中，我们将扩大和筛选我们内部的独特微生物种子库，用于生产新型抗烟曲霉菌药物。我们已经制定了一个雄心勃勃的目标，找到2-5个有希望的针对烟曲霉菌的抗真菌候选药物，为制药业的进一步投资提供了一个令人信服的案例，通过每种化合物初始资产价值为1200万GB的许可交易。

Over 150Mn people are affected by severe fungal diseases each year with 1.7Mn deaths globally. The most severe infections include invasive aspergillosis (IA): a major healthcare-associated infection with mortality rates of up to 95%.Current therapeutic options for IA are limited to three drug classes with low efficacy, severe adverse effects, and high treatment burden. The treatment cycle for these infections costs £90K in average healthcare spend. With no new antifungals classes entering the market in the last 20 years, there is an urgent need for new antifungal treatment options to combat aspergillosis infections and a major market opportunity to develop new solutions against fungal infections more broadly.Two-thirds of the classes of antifungals used in the clinic derive from the ~1% of microbes that can be readily cultured in the laboratory. This bioresource has now been exhausted for novel antifungals and efforts to discover new synthetic solutions have failed to fill the gap. Accessing the remaining 99% of uncultured microbes represents the best opportunity to discover new antifungals.Bactobio has developed a platform combining synthetic biology, next-generation sequencing, and machine learning to culture previously unculturable microbes. So far, we have gained exclusive access to ?1,500 novel and unexplored microbial species. In this project, we will expand and screen our in-house library of unique microbial species for the production of novel antifungals against _A. fumigatus_. We have set an ambitious goal to find 2-5 promising antifungal candidates targeting _A.fumigatus_, providing a compelling case for further investment from the pharmaceutical industry through licensing deals with an initial asset value of £12Mn per compound.