Developing biotherapeutics has been a challenge for many years, possibly going back to the earliest studies on insulin by Banting and Best in the 1920s. On the face of it, biotherapeutics should not be good candidates for medicine; they are much more labile than small molecule therapies. They are difficult to administer and have a tendency to be antigenic in their native state. They are expensive to produce and can present major problems with respect to patenting. They do, however, have several great advantages over small molecule therapies with respect to their phenomenal selectivity and potency. In addition, they open up areas of therapy that would previously have been viewed as undruggable by normal medicinal chemistry standards. This newsletter deals with some of the more recent developments in biotherapeutics, including the very ‘hot’ topic of antibody-drug conjugates to the equally ‘hot’ but somewhat different field of peptide biotherapeutics. Finally, we present an excellent review on crystallographic developments on the structure of hepatitis C virus and how this can assist the development of vaccines in the future.
The free downloads available in this newsletter highlight some of the most recent developments in therapeutic development in drug discovery. I will elaborate on them below.
The first article, by Heidi L. Perez, Pina M. Cardarelli, Shrikant Deshpande, Sanjeev Gangwar, Gretchen M. Schroeder, Gregory D. Vite and Robert M. Borzilleri of Bristol Myers Squibb, entitled “Current status and future directions for antibody-drug conjugates” overviews how such molecules take advantage of the exquisite selectivity of monoclonal antibodies have against their target to recognize and bind to their target and deliver a toxic payload of a conjugated chemical entity to cancer cells. The article deals with the history, current status and future prospects for such therapies.
The second article, from Keld Fosgerau and Torsten Hoffmann of Zealand Pharma A/S, Copenhagen, Denmark, entitled: “Peptide therapeutics - Current status and future directions” outlines how peptide therapies have a history of good selectivity, affinity and are well-tolerated. The renaissance in peptides as therapeutic agents is evident since, at the time of writing, there were 140 agents in clinical trials. They show a SWOT analysis of therapeutic peptides and outline the discovery, design and development of novel peptide-based therapeutic agents. They go on to expand on emerging areas for peptide therapies and technologies to facilitate development in the future.
Finally, is the review from Matteo Castelli, Nicola Clementi1, Giuseppe A. Sautto, Jennifer Pfaff, Kristen M. Kahle, Trevor Barnes, Benjamin J. Doranz, Matteo Dal Peraro, Massimo Clementi, Roberto Burioni and Nicasio Mancini of various institutes in Italy, the United States and Switzerland, entitled, “HCV E2 core structures and mAbs: something is still missing”. The authors discuss how the lack of structural information on hepatitis C virus (HCV) surface proteins has hampered the development of effective vaccines. They do on to describe that despite two recent crystallographic structures on the core of the E2 surface glycoprotein (the primary mediator of HCV entry) the E2 overall structure is still largely unknown and significantly conflict with several biochemical and functional studies performed on E2c structures.
Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 40 peer-reviewed articles, written several book chapters and has held a number of patents. Sadly, since the last newsletter, Steve’s band has fallen out of the World rankings and will not have the opportunity to gain ranking points until they compete in the National Brass Band Championships of Great Britain in September in Cheltenham. A good placing here would surely replace the band in the top 200 in the world and his position in the top 200 second horn players in the world. Register your support by ‘liking’ the Fulham Brass Band’s Facebook page.