The safety of the subject in any clinical trial is of paramount consideration. First in Human studies are special in this case as no data is available on how the investigational product will react in the human body. Preclinical data needs to be adequate to allow translation into a clinical study complying with all medical, scientific, ethical and regulatory aspects. Historical cases have shown that bridging preclinical and clinical is not always been adequate. The gap first needs to be understood and then strategies need to be developed to enable a smooth translation of the preclinical data of “research in animals” to the clinical research with First in Human studies.