Choosing projects based on patient need
All of our drug discovery efforts begin and end with the patient. We determine which diseases to focus our research efforts on based on two questions: Do we have or can we gain significant understanding of the cause or “mechanism” underlying the disease, and does this disease represent a significant unmet medical need in human well-being? If the answer to both questions is “yes,” then we will develop a research program aimed at understanding the disease better and finding a cure.
 

Our early discovery science determines how the disease is caused at a molecular level, using our own new discoveries as well as in collaboration with scientists at many different types of institutions worldwide. We look for clues in both the patients’ experience of the disease and the compendium of medical knowledge that humans have assembled for centuries compiled with the growing knowledge of human biology and genetics. And we design the best possible experiments to test hypotheses and yield answers to unanswered questions about how the disease works and how it can be treated.

Target and compound (or lead) selection
Traditional pharmaceutical development relies heavily on identifying appropriate drug “targets,” i.e., single genes or proteins. As our knowledge of human biology has grown, so has our understanding of what we mean by targets for drug discovery. In fact, we now know that a target may be entire interacting pathways of proteins, which in turn can be at the root of several different and seemingly unrelated diseases. Thus, we concentrate our efforts on discovering or even inventing compounds that can alter the disease-causing mechanism, whether a single protein or a complex pathway of proteins, to bring it back into line with normal function.

Target validation and compound optimization
Once a suitable target and compound are identified, the targets are rigorously “validated,” i.e., proven to be involved in the disease state, and the compounds are “optimized,” i.e., altered in ways that both increase their potential efficacy as well as minimize any potential side effects. The tools of modern chemistry and modern biology merge in these stages to give us the best candidates for the drugs of the future.

“Proof of Concept” trials
Even following this, it is critical that we actually test both the compounds we develop and the mechanisms/targets we identify in actual patients before we can hand off a compound for full development by our pharmaceutical colleagues. Bridging the bench and the clinic with the best expertise from both, we work with our colleagues in development to perform “Proof of Concept” clinical trials. These trials, performed with a small number of patients, are aimed at validating our understanding of mechanism as well as giving us initial data about the efficacy and safety of the compound we have chosen to address that mechanism.

Outlook
This entire process, from target identification through clinical Proof of Concept, takes several years. However, thanks to the advances in genomic and chemical science, that time is growing shorter.
 

In short, our focus on unmet need at the beginning of the process and our rigorous proof-of-concept at the end both minimizes risk and leads to faster and better drugs for the patients, who are at the center of all our efforts.


To learn what happens with a compound once NIBR scientists handed it over to their colleagues in drug development, visit our next page: