Drug development

Question 1

What is target selection?

Answer 1

Could be receptors, enzymes, or transport proteins
then finding a lead by using automated screening against libraries

Question 2

What is lead selection?

Answer 2

Exploratory toxicology and safety, then preclinical development, then clinical development

Question 3

What are the default rodents used?

Answer 3

Rats

Question 4

What are the default non-rodents used?

Answer 4

Beagles

Question 5

What are the three dose groups for toxicology?

Answer 5

Low- no toxicology
Intermediate
High- toxicology expected in target organ

Question 6

What is clinical pathology?

Answer 6

Haematology and clinical chemsitry, kidney and liver function and coagulation

Question 7

What are the goals of non-clinical safety evaluations?

Answer 7

That toxicity is on target and not going anywhere else, that it is reversible, toxicokinetics, maximum toxic dose and minimum affective dose, dose selection for humans and identification of specific monitoring requirements

Question 8

What physiological functions initially have to be investigated for undesirable effects from a drug?

Answer 8

Cardiovascular system
Central nervous system
Respiratory

Question 9

What is the purpose of phase 1 clinical trials?

Answer 9

Finding out if it is safe, how well it is tolderated and what pharmacokinetic properties it has

Question 10

What is the purpose of phase 2 trials?

Answer 10

Finding out how much should be given to be effective and how well the treatment actually works

Question 11

What is the purpose of phase 3 trials?

Answer 11

Has several thousand patients and definitive results are needed, they are multi centre and multi national which makes logistics a lot harder

Question 12

What is the purpose of phase 4 trials?

Answer 12

Post marketing surveillance- when rare or long term adverse effects are detected when it is on the market

Question 13

What is biologics?

Answer 13

Antibody based medicine, vaccines, RNAi, cell based or gene therapy

Question 14

How is selection of a relevant animal model important when using biopharmaceuticals?

Answer 14

Human proteins will cause a large reaction in animals that won’t tell you anything, which is different to small molecules drugs

Question 15

How is the anticipation of risk different for biopharmaceuticals compared to small molecule drugs?

Answer 15

Thourough understanding of the infusion reaction and the cytokine storm is needed
Cytokine release syndrome

Question 16

How is cytokine release syndrome prevented?

Answer 16

Receptor interaction and occupancy must be measured in preclinical trials
drug can’t be given to large groups of people at once

Question 17

What is immunotherapy?

Answer 17

Form of cancer treatment that uses the immune system to attack cancer cells in the same way it would attack bacteria or a virus

Question 18

What are checkpoint inhibitors?

Answer 18

Releasing a natural brake on your immune system so that T cells can recognise and attack tumours

Question 19

What is CAR T cell therapy?

Answer 19

Chimeric antigen receptor therapy- scientists engineer a patients own immune cells to make a new protein which turns them into supercharged cancer fighters

Question 20

What is IL-2?

Answer 20

Growth factor of T cells and white blood cells
Used as immunotherapy until it was found it harmed the patients more than the cancer itself