Dose Selection (early stage) – Vernalis

Invicro UK (formerly Imanova) worked with Vernalis, a biotech company, on a drug candidate targeting the Adenosine A2A receptor for treatment of neurological disorders, which demonstrated how imaging can be used to provide early information in man and reduce both the cost and time of entering proof-of-concept studies. In this instance, a suitable PET ligand, [11C]SCH4424, had already been reported in the literature but needed to be implemented at Invicro UK to a GMP standard.

Using an adaptive study design, the PET study was carried out in parallel with the single ascending dose (SAD) study to relate occupancy at the A2A receptor in the brain with drug dose and plasma concentration. For each drug dose, A2A receptor occupancy was calculated for 2 plasma drug levels.

The data generated clearly demonstrated the relationship between plasma concentration and receptor occupancy in the CNS showing that the drug crosses the blood brain barrier and interacts with the target receptor. Using this data, Vernalis was able to take the drug into further development. Importantly, the quantitative data generated from imaging was used to determine the dose to be used in patient studies for efficacy, thus reducing the number of doses to be tested, saving considerable time and money.

This study clearly demonstrates the value imaging can add to aid decisions about drug development. In this way, imaging holds the key to reducing time and costs of drug development overall.