LNP Formulation Screening, A CDMO Perspective
Umberto Romeo, Head of R&D, Corden Pharma Caponago
Umberto Romeo has 15+ years of experience in drug product process design, development and manufacturing of chemical and biological compounds throughout all stages of development up to commercialization. He is currently the Head of R&D at Corden Pharma Caponago site leading formulation (including LNP Assembly and Downstream) development, analytical development, validation and industrialization activities for injectable drug products as well as clinical manufacturing operations and MS&T. Prior to his current role, he worked as Project and Alliance Manager in Evotec managing complex projects (from Discovery to Phase 3) to successful completion, covering all phases of the project management process (initiation, planning, execution, monitoring and control, and closure) leading project teams to deliver results within the constraints of schedule.
He worked in UCB as Drug Product Process Design and Development Principal Scientist where he was responsible of CMC development activities of Biopharmaceuticals, with a focus on Drug Product Process Design, Development and Technology Transfer to GMP manufacturing sites. During his mission he established Drug Product Process Design and Development department leading a team of 6 people and supporting the CMC development program of the whole UCB biological pipeline.
He worked in Patheon Inc. as Technology Transfer-Project Manager where he managed successfully the technology transfer of more than 15 drug product manufacturing processes of oral, injectable lyophilized and liquid drug products for European, US, Japanese and ROW markets at Phase 3 /commercial scale into Monza manufacturing plant.
Umberto graduated with a degree in Pharmaceutical Biotechnologies in Milano State University.
Nanoparticles have been extensively investigated for drug delivery for decades. Lipid-based nanoparticles such as liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) have demonstrated tremendous clinical success in delivering both hydrophobic and hydrophilic therapeutics.Particularly, lipid nanoparticles (LNPs) have been recognized as an ideal carrier for nucleic acids like DNA, mRNA, and different synthetic oligonucleotides such as siRNA, saRNA, miRNA and other regulatory RNAs, due to their outstanding biocompatibility, biodegradability, and entrapment efficiency. ONPATTRO (Patisiran) is the first approved double-stranded small interfering RNA delivering LNP (2018).RNA therapeutics have shown potential in various medical applications, including virus vaccines, cancer immunotherapy, and gene editing. The need of drug delivery vehicles including lipid nanoparticles (LNP) for RNA therapeutics have been developed because of the instability of RNA. Currently, ionizable lipids are considered as crucial components of LNP-based RNA therapeutics because they are positively charged at a low pH to enhance the encapsulation of negatively charged RNA, and the charge becomes less positive or almost neutral at physiological pH (~7.4), to reduce the toxicity 5. In addition, various mRNA engineering methods have been developed to enhance the stability and the translation efficacy of mRNA therapeutics, such as a selection of untranslated regions (UTRs), addition of a poly-A tail, capping, and nucleoside modification 6. Based on these advanced techniques, two LNP-based mRNA vaccines (BNT 162b2, Pfizer-BioNTech; and mRNA-1273, Moderna) were successfully developed and obtained authorization from regulatory agencies in 2020 in multiple countries 7. Additionally, multiple types of LNP-based RNA therapeutics are under active investigation to treat various infectious diseases and cancers. CordenPharma played an important role during the Covid-19 pandemic response, ramping up its lipid manufacturing capacity across multiple sites to support the global demand of GMP grade lipids needed for the manufacture of Moderna’s Spikevax™ vaccine.Acknowledging the importance of LNPs as non-viral based delivery systems with the potential to revolutionize the current standard of medical therapy for a multitude of disease as well as enabling new therapeutic strategies for unmet clinical needs, CordenPharma initiated in late 2021 a strategic investment program at our Sterile Injectable site CordenPharma Caponago (Italy) to establish LNP formulation development and cGMP manufacturing capabilities to support an promote fastrack Nanoparticles-based drug development for our partners globally.Exploiting our state of the art technologies we demonstrated through the planning and execution of a pilot study to be able to reproduce commercially viable LNP formulations such as the ones used for the COVID-19 vaccines, but as well novel LNP formulations usable in a pre-clinical and eventually clinical setting through the assessment of the efficacy in terms of encapsulation efficiency (EE%) and transfection capability in different cell lines.The present discussion will be focused on the evaluation of the data generated through the aforementioned pilot study.In the wake of the obtained results, we’ve already started to create much more combinations of lipidic mixtures to formulate new LNPs that will be fully characterized and tested as well, with the aim of creating a wide library of LNPs with specific physical and biological characteristics to be eventually progressed in pre-clinical and clinical development in in collaboration with our partners.
