Head of Technical and Pharmaceutical Operations, MedinCell
Formulation Development for Long Acting Injectables of Fragile Molecules - BEPO: A Game-Changing Delivery System
Peptides and proteins have become more and more attractive drugs in the last decades, due to their selectivity, their high bioactivity and low toxicity. These drugs have been successfully developed for the treatment of major diseases like e.g. type-2 diabetes, cardiovascular disorders, various types of cancer and autoimmune diseases. However, these fragile molecules remain very difficult-to-administer drugs, due to their poor stability in formulation processes, their enzymatic degradation and poor absorption across epithelial membranes , as well as their short plasma half-life. At the present time, peptides are predominantly administered via injection, using long-acting formulations mainly based on biodegradable poly (lactic acid – co - glycolic acid) (PLGA) copolymer microspheres or implants slowly releasing the peptide over weeks or months. These formulations have become the most successful injectable peptide formulations on the market . These technologies however still show many drawbacks related to complex reconstitution procedures before administration or the need of large gauge needles for injection. They have also proven to be totally inappropriate for producing long-acting protein formulations due to in-process and storage stability issues of the proteins. In this context, the BEPO® in situ implant forming (ISIF) technology based on the association of amphiphilic block poly (lactic acid) (PLA) - poly (ethylene glycol) (PEG) copolymers appears to provide a unique combination for ease of administration, stability of fragile molecules and in vivo control of the drug release rate and duration of action after injection. This talk will provide insight into the many advantages of this new, highly versatile, long-acting injectable formulation technology and present the promising results obtained for the controlled delivery of a small, bispecific short half-life antibody for immunotherapy in prostate cancer . Indeed, the antibody remains functional and active through formulation and release processes and demonstrates high anti-tumor activity in animal models, while improving subcutaneous bioavailability and half-life of the biomolecule.
1 - Challenges in oral peptide delivery: lessons learnt from the clinic and future prospects; Therapeutic Delivery (2017) 8(8), 663-684 - J. Richard
2 - Challenges in the delivery of peptide drugs: an industry perspective; Therapeutic Delivery (2015) 6(2), 149-163 - A.L. Lewis, J. Richard
3 - Anti-PSMA/CD3 bispecific antibody delivery and anti-tumor activity using a polymeric depot formulation; Molecular Cancer Therapeutics (2018) 17(9),1927-1940 - W. Leconet et al.
Dr Joël Richard is currently Head of Technical & Pharmaceutical Operations at MedinCell (Montpellier, France). He is leading all the pharmaceutical development and non-clinical pharmaco/toxico-kinetic activities of the company, specialized in the development of Long-Acting Injectables. (LAIs), using the proprietary technology BEPO®. Dr Richard has 30 years of experience in chemistry and biopharmaceutical R&D, including several global senior positions in various Biotech and Pharma companies, such as:
- Senior Vice President, Pharmaceutical Development – Peptides in Ipsen (France),
- Vice President, Drug Product Development in Ipsen (France),
- Director, Pharmaceutical Development in Serono and Merck Serono (Italy, Germany),
- Vice President Research, and Europe R&D Director at Ethypharm (France),
- COO at Mainelab (France), a drug delivery company he co-founded, which was specialized in developing solvent-free processes for protein delivery systems.
Since 1996, Dr Richard has focused his research activity on new formulation technologies and drug delivery systems (such as microspheres, nanosystems, gelling systems, chemically-modified proteins, supercritical fluid technology . . .), especially for injectable peptide and protein formulations. Dr Richard has graduated from Ecole Normale Supérieure (Cachan, France). He has got a PhD in Materials Science from University of Paris, France, and the “Habilitation à Diriger les Recherches” degree in Chemistry from University of Bordeaux I. He has published 68 peer-reviewed scientific papers, 8 book chapters and 2 review editorials in various fields (colloids and interfaces, drug delivery systems, supercritical fluids, protein formulations, nanoparticles). He is the author of more than 140 international communications and 55 patent families