Therapeutics


Antibody molecule. Molecular structure of a monoclonal human immunoglobulin


(IgG2a). IgG antibodies are composed of two long heavy chains and two shorter light chains. This antibody adopts a T-shape: the arms of the T


make up the Fab or antigen binding region, while the base part or Fc region plays a role in interacting with the immune system. Under the name of Denosumab this type of human monoclonal antibody is used for the treatment of osteoporosis, treatment- induced bone loss and bone metastases. Image courtesy of Alfred Pasieka/


Science Photo Library


expense allocations. By outsourcing one or more stages of the drug path, from discovery through human trials, pharma companies reap the benefit of dedicated expertise without incurring the over- head. Now, pharma companies are thinking differ- ently about the types of therapeutics to fill their product and profit pipelines and, interestingly, a significant majority of pipelined drugs are coming from small companies, who collaborate and grant licensing agreements with large pharmaceutical companies. Some of the major pharma players with blockbuster biologicals include AbbVie, Roche, Sanofi, Janssen and Pfizer. This shift has accompanied better compound enrolment into clinical trials as well, which translates to more effective and generally safer therapies compared to traditional chemically-derived small molecules. As history shows, there is no ‘silver bullet’ cure or single method for success. Biological medicines represent a mainstay to current therapies for a mul- titude of diseases. However, as they are more struc- turally complex in nature and hypersensitive to manufacturing conditions, they are difficult to char- acterise and produce. They inherently exhibit phys- iochemical differences, and any change in manufac- turing could potentially result in a significant varia- tion in not only the processes (ie purification meth- ods) used for biological production, but also to dif- ferences in the product characteristics for quality, such as stability and structure2. Similarly, any


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change in quality also affects function, including therapeutic efficacy, immune response, patient tol- erance and outcome. Thus, finding the ‘needle in the haystack’, and manufacturing biologicals while meeting the needs of globalisation requirements involves significant time and financial resources. Small companies, academics and contract research organisations (CROs) alike are now interfacing in the biologicals sector of the market where they are quickly progressing the industry by combining their technical expertise and sharing their knowledge of biology and chemistry with the clinicians in a col- laborative model. The area of monoclonal antibodies (mAbs) has significantly grown for drug discovery research and development. As biologics have considerable therapeutic specificity and benefits, some believe that these biological pharmaceuticals may be the greatest among all human medicines. Biotherapeutics have shown to have extremely high potency and target biomarkers responsible for pathology and disease, which makes it very attrac- tive from a patient perspective, as dosing is lower than traditional therapies. This, in turn, translates to lower toxicity and reduced potential for side- effects, since the proteins do not show any mam- malian pharmacological activity once metabolised into fragments by the human body. The majority of the fragments also do not display any residue sig- nature of the active substance. Moreover, the high


Drug Discovery World Summer 2017


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