Paclitaxel-loaded biodegradable microparticle production optimised on a microfluidics platform

"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."