Glossary

Anaesthesia: Anaesthesia is characterised by unconsciousness resulting from the administration of a general anaesthetic, normally together with a strong analgesic, to facilitate otherwise very painful procedures. Apart from the loss of consciousness also pain perception, defensive reflexes as well as muscle tension are thereby inactivated throughout the body.

Anaesthetic: A drug which effects anaesthesia/narcosis.

Clinical Phase I: In clinical Phase I studies, drug candidates are explored in healthy volunteers (so-called probands). The main focus of these studies is usually safety and tolerability. Moreover, the concentration of the substance in the blood is typically being determined, among other parameters. Interaction with other drugs is also frequently studied. Potential participants freely decide about inclusion in Phase I studies after being informed about scope, risks and the study protocol.

Clinical Phase II: In clinical Phase II studies drug candidates are for the first time therapeutically evaluated in patients. A successful Phase II thus is considered a major step forward regarding the commercial valuation of the drug and the company developing it. Phase II studies mainly focus on finding the right dose for effective therapy. While statistical significance usually is achieved through larger scale Phase III studies, Phase II studies often give important indications whether the drug candidate can meet expectations. In most cases, if major side effects exist, they will be discovered in Phase II. Potential participants or their relatives, respectively, freely decide about inclusion in Phase II or III studies after being informed about scope, risks and the study protocol.

Clinical Phase III: Clinical Phase III studies concentrate on showing efficacy in a statistically significant manner with an acceptable safety profile. In Phase III and sometimes already in Phase II , studies are normally carried out as double-blind, placebo controlled trials. “Placebo control” refers to the fact that one sub-group of patients receives only an inactive substance (placebo) in combination with test drug. As neither the patient nor the physician knows who received drug candidate or placebo, these studies are dubbed “double-blind”. Through this study design, one can rule out that measured effects are due to other factors than the drug candidate. Potential participants or their relatives, respectively, freely decide about inclusion in Phase III studies after being informed about scope, risks and the study protocol. After successful completion of Phase III , the next step is usually filing for regulatory approval.

Clinical studies: Well-controlled assessment of the effects of drug candidates or new medical devices.

GGF2: Glial Growth Factor 2; known to stimulate the growth and differentiation of a variety of cells including glial cells, the support cells of the nervous system. These glial cells form the myelin sheath that insulates nerve cells and is essential for their survival and proper functioning. In demyelinating diseases such as multiple sclerosis, the myelin sheath is damaged, leading to the degeneration of nerve cells.

Haemophilia: Caused by a lack of certain coagulation factors, mostly Factor VIII and, less frequently Factor IX. Such deficiency results in less clotting but also increased fibrinolysis. This results in the inability to form stable blood clots when blood vessels are damaged leading to prolonged and recurrent bleeding.

INN (international non-proprietary name): The non-proprietary or generic name given to a pharmaceutical substance by the World Health Organisation (WHO). Whereas many substances are distributed under different trade names, INN s are
internationally uniform and thereby facilitate a clear distinction. In contrast to internal substance names used by companies (e.g. CNS 7056), it is custom to use the INN in scientific publications (i.e. Remimazolam).

Morphine-6-Glucuronide (M6G): A highly potent opiate which may offer therapeutic advantages over morphine, the current gold standard for the treatment of moderate to severe post-operative pain, in having an equivalent analgesic effect, but with a reduced tendency to cause side-effects such as nausea and vomiting.

Narcotic: A drug which effects anaesthesia/narcosis.

Opiate: Any of various sedative narcotics containing opium or one or more of its natural or synthetic derivatives.

Peri-operative pain: Pain experienced during and/or after an operation, originating from the surgery.

Placebo: Inactive substance. In clinical studies one patient group receives an inactive substance (placebo) instead of the drug candidate in order to rule out that effects are caused by other factors than the drug.

Pre-clinical research: Laboratory tests of a new drug candidate or a new medical device on animals or cell cultures. These tests are conducted to explore the mode of action as well as to detect potential risks prior to testing in humans.

Proband: Volunteer (Phase I studies)

Remimazolam: A new short-acting sedative and general anaesthetic. After intravenous administration to patients participating in clinical studies, Remimazolam rapidly induces sedation. It has the potential to be developed as
a sedative agent for day case procedures, the induction and maintenance of anaesthesia and as a sedative for mechanical ventilation in the Intensive Care Unit (ICU).

Sedation: Reduction of anxiety, stress, irritability, or excitement by administration of a sedative to facilitate a medical procedure.

Sedative: A drug which generally promotes sedation.

Solulin: A soluble variant of thrombomodulin under investigation by PAION which may act as an “intelligent anticoagulant” with anti-inflammatory potential which could be useful for the treatment of thrombo-embolic diseases such as haemophilia.

Thrombomodulin: Key factor in coagulation. By inhibiting certain steps in the coagulation cascade, it has antithrombotic effects. PAION’s Solulin is a soluble variant of thrombomodulin.