Small molecules have always formed the basis of drug development. They still do but biologics have begun taking a definitive role. Biologics are defined to be derived from natural sources and can take the form of whole blood and organs, proteins, stem cells, antibodies, antigens, interfering RNA and viruses for gene therapy. In contrast to small molecules which have known structures, and are manufactured by chemical processes, biologics are heterogenous, complex and more challenging to synthesize. A simple picture demonstrates their complexity:
Despite their complexity, biologics have proven extremely essential for treatments of various debilitating diseases. Perhaps the most well-known example would be insulin, the hormone secreted by the pancreatic islet cells which lowers blood glucose levels. This hormone was initially isolated from cattle and pigs and injected into patients suffering from diabetes to lower their blood sugar levels. This created a fair share of problems due to human allergic responses but was overcome in 1978 by scientists at Genentech that were able to produce human insulin using our good old trusty bacteria, E. coli.
Since then, there have been many more biologics approved for treatment. Perhaps the greatest proportion are represented by monoclonal antibodies, with over 300 in development and 32 approved for treatment. Most of them target cancer, autoimmune disease and infectious diseases (see pie chart). The exponential increase of monoclonal antibody therapeutics may be attributed to the rapid technological advancements involved in their engineering, production, and screening against various targets. One of the key movers and shakers in developing monoclonal antibody therapies is Munich-based Morphosys AG (http://www.morphosys.com/). They have the industry’s largest fragment antibody library and utilize phage display techniques for screening selective binders and humanized mice to generate high-affinity specific monoclonal antibodies. Perhaps the numbers speak for themselves: 90 antibodies in development and 22 already in clinical trials. It is interesting to see a company that consistently innovates (and are not afraid of shedding staff from 420 in 2012 to a trim 299 in 2013) and acquires new technologies to advance a focused goal, in this case, producing quality antibodies against specific targets.
These are exciting times with promising novel technologies ahead, one being the use of bispecific antibodies, offering some hope to the bleak and barren landscape that small molecule therapy is currently facing.
*Images taken from Medicines in Development -Biologics 2013 report http://www.phrma.org/sites/default/files/pdf/biologicsoverview2013.pdf