Summary preclinical drug research
Introduction
Phase in drug discovery and development
• chemicals = small molecules
— In the early days, we talked about small molecules
— Most drugs on the market are small molecules
— E.g.: aspirin, fluoxetine, omeprazole, ...
— !! for several diseases small molecules are not the right option → solution:
biopharmaceuricals
• Natural products = complex molecules
— We also have natural products → cancer medication coming from plants for example
— E.g.: artemether, paclitaxel, vinblastine, …
• Biologicals = large (complex) molecules
— E.g.: insulin, interferon, EPO, ...
Some facts and figures
Slide 8: R&D spending in different industry sectors
• Biopharmaceuticals = specific for the human target and that’s why there are less side effects
• Competition is very high
• If you working in the biopharmaceutical field this is very expensive (large cost)
Slide 9: R&D spending & therapeutic areas
• Limited number of patients = orphan diseases (= rare disease)
— you will earn less when you sell a product for a rare disease than when you sell a drug
for a common disease
— In some cases (small target population) the price needs to be high because it cost a lot
to make the drug
• In the early years was there a lot of cost, lot of sales + high number of approvals → FDA
approvals is now less
• (slide 11) Japan: smaller country so the expenditure is smaller
• Full cost of a drug: over the years has it become more expensive to get a drug on the market
o More than 1 billion dollars → explains why companies want to gain money with the
drug
o If they don’t proceed with the production it is important they do this early = fast, fail
cheap
Slide 13 → very clear that a lot of the cost go to the clinical trials
• Phase I clinical trials = volunteers = most of the time, these are young, healthy men (students)
→ you want to reach a certain concentration (most of the time, this works)
— No female students: companies don’t want to risk that women will be infertile or that
you will expose the foetus (if she don’t know she is pregnant)
— The risk on issues with the male volunteer is less
+ you need to collect less non clinical data for the men
• Phase II = you want to know the efficacy of the drug in a patient population
— Phase II a = small group
— Phase II b = bigger group
• Phase III = very large clinical trials → you need several sites to have enough people
— Phase 3 has a multisite environment → multiple facilities around the world (and the
location depends on where you find patients). Sometimes hard to recruit patients
, — If this goes right, you get approval to bring the drugs on the market
• After this, you need to do follow-up
Slide 14: annual population growth rates
• Numbers count !! → if a huge population has a certain disease, that means cash
• It’s ideal that you have a lot of patients → you will make a lot of money
• Economic situation in the region is also important
— In China: huge boost of pharmaceutical industry
o Economic situation has improved → they set up their own pharmaceutical
companies → huge competition with this new power governments
— Same in Brazil but now the economic situation is going down there is less investment
• Graph changes over the year → economic situation has a important role
• Some indications are more prominent in a certain region → can be a driver
Slide 15: healthcare spending in relation to age
• The elder take more medications
— Attention for underdose and adverse effects
o today there are several patients that are underdosed because of risk or
because of interference with other drugs → needs to be studied
slide 16: development costs and revenue cycle
• About 2 billion dollars to get a drug on the market (a little bit variation)
• Not a lot of investment in:
— Orphan disease: occurring in a small number of patients
o Different between regions and also the number of patients that you need to
be classified as orphan diseases is different
o Pharmaceutical industries are not interested in this → less money for them
▪ Government and foundations providing finances for theses drug
development for these diseases
— Neglected diseases
• Cash flow
— Hopefully when you launch you drug you will see that your sales explode
— Many drugs stay in the first phase (first purple line (=investment)) and fail
— Drop at the end = patent expire → there are companies that are there to bring a
generic drug after the patent of another company expires
slide 17: pharmaceutical sales by region
• US is the front runner
• China is an emerging market
slide 18: blockbuster drugs
• Blockbuster = sales > 1 billion US dollar/ year
• Humira is one of the best sold drugs → 20 billion US dollar/year
• Many blockbuster drugs come of large pharmaceutical companies
• There are small companies but they can’t spend 1 billion dollar on drug development → large
companies buy the biotech company or just the product if they believe that a certain drug has
a high potential
slide 19: top drug launches 2019
• We see an increase of biopharmaceuticals
, • Mab: monoclonal Ab
• We have gene therapy popping up
• Price setting is different for every country
Slide 20: timelines of drug development
• Normally it takes up to 12 year to get your drug to the market
• You start quite early + apply quite early for your patent (after 2 or 3 years)
• The faster you get to the market, the more money you can get → most of the time you have 5
to 8 years left before the patent expires
— Patent can be prolonged for 5 years → for very specific drugs, but most of the time this
is not done
Slide 22: challenges for pharma industry
• Generic competition
• Price containment
— Several governments look critical to the price setting → they negotiate for lower price
setting
• Poor product differentiation
• Increased competition from “me-too” drugs
• Parallel importation
• Counterfeiting of drugs
• If you have a certain drug it should be better than one already on the market
• A lot of drugs are similar. You get a dilution of your revenue.
Slide 23: product positioning
• Arrows
— Sales volume is quite important → this goes from low to high
— Level of competition can also be low or high
— Unit sales value of a product
o Paracetamol pill will be very cheap
o Immunotherapy drug will be very costly
— Medical differentiation: whether you can really position your drug for unique
indication
• Generics
— Lowly priced drugs → volume is important → so it is a large market
— There is a lot of competition
— Low differentiation
• Mega blockbusters → somewhere in the middle
— Good sales
— Medium level of competition (not too much)
— Good price setting
— Relatively good medical differentiation
• Targeted therapeutics = niche markets
— Very high medical differentiation = specific indication & no other drugs
— You don’t need a high sales because you can get your price setting high → you will still
make a lot of money
, Slide 24: failure rates in drug development
• Highest failure in the non-clinical part and in the clinical part early
• Reasons
— Non-clinical: bad pharmaceunetics
— Phase 1: bad properties for example (not enough exposure or absorption)
— Phase 2: mainly because it is not effective
— Phase 3: you don’t want this, but it still happens
o When you exposure a large group and you have a lot of people that don’t
response
— Regulatory: they don’t approve your medication → you lose all your money
— Approved: you get post marketing problems
o Companies need post marketing surveillance
— Competition can also be a reason to stop your drug development
Slide 25: major therapeutic areas
• Pharmaceutical targets
— Small molecules target often receptors (to activate or to inhibit)
— GPCR, transporters (certain brain diseases), enzymes (bv. cib inhibitors), antiviral,
antibacterial
• You also see a lot of drug development for the rare diseases
Slide 26: biotechnology-derived medicines
• Oligonucleotides : small sequence of nucleotides to target certain mRNA
— Inhibit translation to protein → can be important for cancer
• A lot of focus on these RNA therapeutics and you will target a specific sequence to have less
adverse effects
Slide 27 – 37: major pharmaceutical companies + biotech companies
Drug discovery process – therapeutic modalities
Types of therapeutics
• Conventional therapeutics = all types of intervention aimed at alleviating the effects of disease
— Improve disease symptoms and/or prognosis
— Alleviate effects of existing disease
— Directed towards disease prevention
— Achieve permanent cure
• Non-conventional health products
— Nutraceuticals = range of dietary preparations
o slimming diets, diets with minerals, vitamins, fiber, antioxidants, ...
o some scientific rationale
o not subjected to formal regulatory approval
▪ Ceuticals are often not regulated. Sold you as products to help to lose
weight, for example
▪ In the end you can’t be sure what the effect/benefit is of
nutraceuticals
▪ Also safety is not sure
— Cosmeceuticals = cosmetics supplemented with some active (?) substances
o reduce skin wrinkles, promote hair growth, ...
o little or no scientific rationale
o free sales (but major market !!) → lot of publicity
Introduction
Phase in drug discovery and development
• chemicals = small molecules
— In the early days, we talked about small molecules
— Most drugs on the market are small molecules
— E.g.: aspirin, fluoxetine, omeprazole, ...
— !! for several diseases small molecules are not the right option → solution:
biopharmaceuricals
• Natural products = complex molecules
— We also have natural products → cancer medication coming from plants for example
— E.g.: artemether, paclitaxel, vinblastine, …
• Biologicals = large (complex) molecules
— E.g.: insulin, interferon, EPO, ...
Some facts and figures
Slide 8: R&D spending in different industry sectors
• Biopharmaceuticals = specific for the human target and that’s why there are less side effects
• Competition is very high
• If you working in the biopharmaceutical field this is very expensive (large cost)
Slide 9: R&D spending & therapeutic areas
• Limited number of patients = orphan diseases (= rare disease)
— you will earn less when you sell a product for a rare disease than when you sell a drug
for a common disease
— In some cases (small target population) the price needs to be high because it cost a lot
to make the drug
• In the early years was there a lot of cost, lot of sales + high number of approvals → FDA
approvals is now less
• (slide 11) Japan: smaller country so the expenditure is smaller
• Full cost of a drug: over the years has it become more expensive to get a drug on the market
o More than 1 billion dollars → explains why companies want to gain money with the
drug
o If they don’t proceed with the production it is important they do this early = fast, fail
cheap
Slide 13 → very clear that a lot of the cost go to the clinical trials
• Phase I clinical trials = volunteers = most of the time, these are young, healthy men (students)
→ you want to reach a certain concentration (most of the time, this works)
— No female students: companies don’t want to risk that women will be infertile or that
you will expose the foetus (if she don’t know she is pregnant)
— The risk on issues with the male volunteer is less
+ you need to collect less non clinical data for the men
• Phase II = you want to know the efficacy of the drug in a patient population
— Phase II a = small group
— Phase II b = bigger group
• Phase III = very large clinical trials → you need several sites to have enough people
— Phase 3 has a multisite environment → multiple facilities around the world (and the
location depends on where you find patients). Sometimes hard to recruit patients
, — If this goes right, you get approval to bring the drugs on the market
• After this, you need to do follow-up
Slide 14: annual population growth rates
• Numbers count !! → if a huge population has a certain disease, that means cash
• It’s ideal that you have a lot of patients → you will make a lot of money
• Economic situation in the region is also important
— In China: huge boost of pharmaceutical industry
o Economic situation has improved → they set up their own pharmaceutical
companies → huge competition with this new power governments
— Same in Brazil but now the economic situation is going down there is less investment
• Graph changes over the year → economic situation has a important role
• Some indications are more prominent in a certain region → can be a driver
Slide 15: healthcare spending in relation to age
• The elder take more medications
— Attention for underdose and adverse effects
o today there are several patients that are underdosed because of risk or
because of interference with other drugs → needs to be studied
slide 16: development costs and revenue cycle
• About 2 billion dollars to get a drug on the market (a little bit variation)
• Not a lot of investment in:
— Orphan disease: occurring in a small number of patients
o Different between regions and also the number of patients that you need to
be classified as orphan diseases is different
o Pharmaceutical industries are not interested in this → less money for them
▪ Government and foundations providing finances for theses drug
development for these diseases
— Neglected diseases
• Cash flow
— Hopefully when you launch you drug you will see that your sales explode
— Many drugs stay in the first phase (first purple line (=investment)) and fail
— Drop at the end = patent expire → there are companies that are there to bring a
generic drug after the patent of another company expires
slide 17: pharmaceutical sales by region
• US is the front runner
• China is an emerging market
slide 18: blockbuster drugs
• Blockbuster = sales > 1 billion US dollar/ year
• Humira is one of the best sold drugs → 20 billion US dollar/year
• Many blockbuster drugs come of large pharmaceutical companies
• There are small companies but they can’t spend 1 billion dollar on drug development → large
companies buy the biotech company or just the product if they believe that a certain drug has
a high potential
slide 19: top drug launches 2019
• We see an increase of biopharmaceuticals
, • Mab: monoclonal Ab
• We have gene therapy popping up
• Price setting is different for every country
Slide 20: timelines of drug development
• Normally it takes up to 12 year to get your drug to the market
• You start quite early + apply quite early for your patent (after 2 or 3 years)
• The faster you get to the market, the more money you can get → most of the time you have 5
to 8 years left before the patent expires
— Patent can be prolonged for 5 years → for very specific drugs, but most of the time this
is not done
Slide 22: challenges for pharma industry
• Generic competition
• Price containment
— Several governments look critical to the price setting → they negotiate for lower price
setting
• Poor product differentiation
• Increased competition from “me-too” drugs
• Parallel importation
• Counterfeiting of drugs
• If you have a certain drug it should be better than one already on the market
• A lot of drugs are similar. You get a dilution of your revenue.
Slide 23: product positioning
• Arrows
— Sales volume is quite important → this goes from low to high
— Level of competition can also be low or high
— Unit sales value of a product
o Paracetamol pill will be very cheap
o Immunotherapy drug will be very costly
— Medical differentiation: whether you can really position your drug for unique
indication
• Generics
— Lowly priced drugs → volume is important → so it is a large market
— There is a lot of competition
— Low differentiation
• Mega blockbusters → somewhere in the middle
— Good sales
— Medium level of competition (not too much)
— Good price setting
— Relatively good medical differentiation
• Targeted therapeutics = niche markets
— Very high medical differentiation = specific indication & no other drugs
— You don’t need a high sales because you can get your price setting high → you will still
make a lot of money
, Slide 24: failure rates in drug development
• Highest failure in the non-clinical part and in the clinical part early
• Reasons
— Non-clinical: bad pharmaceunetics
— Phase 1: bad properties for example (not enough exposure or absorption)
— Phase 2: mainly because it is not effective
— Phase 3: you don’t want this, but it still happens
o When you exposure a large group and you have a lot of people that don’t
response
— Regulatory: they don’t approve your medication → you lose all your money
— Approved: you get post marketing problems
o Companies need post marketing surveillance
— Competition can also be a reason to stop your drug development
Slide 25: major therapeutic areas
• Pharmaceutical targets
— Small molecules target often receptors (to activate or to inhibit)
— GPCR, transporters (certain brain diseases), enzymes (bv. cib inhibitors), antiviral,
antibacterial
• You also see a lot of drug development for the rare diseases
Slide 26: biotechnology-derived medicines
• Oligonucleotides : small sequence of nucleotides to target certain mRNA
— Inhibit translation to protein → can be important for cancer
• A lot of focus on these RNA therapeutics and you will target a specific sequence to have less
adverse effects
Slide 27 – 37: major pharmaceutical companies + biotech companies
Drug discovery process – therapeutic modalities
Types of therapeutics
• Conventional therapeutics = all types of intervention aimed at alleviating the effects of disease
— Improve disease symptoms and/or prognosis
— Alleviate effects of existing disease
— Directed towards disease prevention
— Achieve permanent cure
• Non-conventional health products
— Nutraceuticals = range of dietary preparations
o slimming diets, diets with minerals, vitamins, fiber, antioxidants, ...
o some scientific rationale
o not subjected to formal regulatory approval
▪ Ceuticals are often not regulated. Sold you as products to help to lose
weight, for example
▪ In the end you can’t be sure what the effect/benefit is of
nutraceuticals
▪ Also safety is not sure
— Cosmeceuticals = cosmetics supplemented with some active (?) substances
o reduce skin wrinkles, promote hair growth, ...
o little or no scientific rationale
o free sales (but major market !!) → lot of publicity
