Paclitaxel-loaded biodegradable microparticle production optimised on a microfluidics platform

“癌症是全球第二大死亡原因，全球有超过800万人死亡(世卫组织，2015年)，英国有163,444人死亡(CRUK，2014年)。对于某些癌症患者，如卵巢癌，仍有大量未得到满足的临床需求，这些患者的中位生存期只有3年。在过去的30年里，这些存活率没有变化。BioMoti与Pharmidex和CPI结成了新的联盟，正在开发Oncojan(Tm)平台，以克服目前的限制。Oncojans(Tm)是一种新型的精确持续治疗药物，它装载在可生物降解的微粒中，并靶向肿瘤上的CD95L。CD95L在肿瘤体积和血管系统的细胞上过度表达(但在健康组织上不表达)，促进增殖、转移和免疫逃避。BMT101是基于Oncojan(Tm)的主要候选药物，即通过CD95R表面修饰的可生物降解的微粒靶向CD95L的化疗。这项建议旨在建立在令人振奋的试点数据的基础上，这些数据表明，BMT101具有显著的临床前活性；与紫杉醇(R)标准护理化疗相比，卵巢癌的肿瘤负担减少了65倍，中位生存期和毒性损失增加了一倍。使该技术进步到成功商业结果的一个主要障碍是能够以有意义的规模可控地制造具有所需属性的微粒。这包括以特定和单分散的尺寸可靠地生产具有高紫杉醇载量的微粒。对于这个项目，我们将研究开发一种可扩展的方案的可行性，以利用微流控技术可重复生产具有理想属性的BMT101配方。我们将验证生产的配方在体外和体内保持高效率，正如在早期的试点研究中看到的那样。其目的是为未来临床试验中符合法规的材料的生产提供一条明确的路线。积极的项目成果将使商业投资能够支持BMT101的未来正式开发，使高度未满足卵巢癌适应症的患者受益。它很可能同样的配方可以用于进一步治疗不当的适应症，如三阴性乳腺癌或食道癌。“

"Cancer is the second leading cause of global mortality with over 8,000,000 deaths worldwide (WHO, 2015) and 163,444 in the UK (CRUK, 2014). There continues to be large unmet clinical need for patients with certain cancers such as ovarian where median survival is only 3 years. These survival rates have not changed for the past 3 decades. BioMoti, in a new alliance with Pharmidex and the CPI, is developing the Oncojan(tm) platform to overcome current limitations. Oncojans(tm) are a new class of precision sustained therapeutics that are loaded in biodegradable microparticles and target CD95L on tumours. CD95L is overexpressed on cells of the tumour bulk and vasculature (but not on healthy tissue) where it promotes proliferation, metastasis and immune evasion. BMT101 is the Oncojan(tm) based lead candidate that is the chemotherapy loaded into biodegradable microparticles surface modified with CD95R to target CD95L. This proposal aims to build on exciting pilot data showing that BMT101 results in remarkable preclinical activity; 65-fold reduction in tumour burden, doubling of median survival and loss of toxicity compared to the Taxol(r) standard-of-care chemotherapy in ovarian cancer.One major barrier to progressing the technology to a successful commercial outcome is the ability to controllably manufacture microparticles with desirable attributes at a meaningful scale. This includes reliably producing microparticles with high paclitaxel loadings at a specific and monodisperse size. For this project, we will study the feasibility of developing a scalable protocol for the reproducible manufacture of BMT101 formulation with desirable attributes using microfluidics technology. We will verify that produced formulations maintain high efficacy in vitro and in vivo as seen in early pilot studies. The aim is to provide a clear route for the future manufacture of regulatory compliant material for clinical trials. Positive project outcomes will enable commercial investment to support future formal development of BMT101 for the benefit of patients in the highly unmet ovarian cancer indication. It is likely the same formulation could be used in further poorly treated indications such as triple negative breast or oesophageal cancer."