Paclitaxel-loaded biodegradable microparticle production optimised on a microfluidics platform

“癌症是全球死亡的第二大原因，全球死亡人数超过8，000，000人（WHO，2015），英国死亡人数为163，444人（CRUK，2014）。对于某些癌症（如卵巢癌，中位生存期仅为3年）患者，仍存在大量未满足的临床需求。这些存活率在过去30年中没有改变。BioMoti与Pharmidex和CPI建立了新的联盟，正在开发Oncojan（TM）平台以克服当前的限制。Oncojans（TM）是一类新的精确持续治疗药物，装载在可生物降解的微粒中，靶向肿瘤上的CD 95 L。CD 95 L在肿瘤块和脉管系统的细胞上过表达（但不在健康组织上），在那里它促进增殖、转移和免疫逃避。BMT 101是基于Oncojan（TM）的主要候选药物，它是装载到表面用CD 95 R修饰的可生物降解微粒中的化疗药物，以靶向CD 95 L。该提案旨在建立在令人兴奋的试点数据基础上，这些数据表明BMT 101具有显著的临床前活性;肿瘤负荷降低65倍，与Taxol（r）标准相比，中位生存期和毒性损失增加了一倍，将该技术进展到成功的商业结果的一个主要障碍是以一定的浓度可控地制造具有期望属性的微粒的能力。有意义的规模。这包括可靠地生产具有特定和单分散尺寸的高紫杉醇负载的微粒。对于这个项目，我们将研究开发一个可扩展的协议的可行性，可重复生产的BMT 101配方所需的属性，使用微流体技术。我们将验证所生产的制剂在体外和体内保持高功效，如在早期试点研究中所见。其目的是为未来生产符合监管要求的临床试验材料提供明确的途径。积极的项目结果将使商业投资能够支持BMT 101的未来正式开发，以使高度未满足的卵巢癌适应症患者受益。同样的制剂可能用于治疗其他治疗不良的适应症，如三阴性乳腺癌或食管癌。"

"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."