TORCHING THE HAYSTACKModels of Drug Development

Dennis Lendrem

Torching the Haystack

•1990• Business Process Reengineering prompted a

reinvention of pharmaceutical development processes. • Minimizing time to market identified as the key to

improving R&D productivity.• By placing development tasks in parallel, wherever

possible, we minimize time to market for successful molecules.

Torching the Haystack

Before Development Speed Initiative

6321 4 5

3

2

1 64

5

After Development Speed Initiative

Time to Market

Torching the Haystack

BUT

Torching the Haystack

MOST …molecules don’t make it to market

10%

Torching the Haystack

• We optimized the R&D process around an event which happens less than 10% of the time.

Torching the Haystack• By placing tasks in parallel to reduce cycle time we

inadvertently:• Increased R&D costs• Increased late-stage attrition rates, and• Increased expected time to market

Lendrem DW, Lendrem BC Torching the Haystack: Modelling fast-fail strategies in drug development. Drug Discov Today. 2013 Apr;18(7-8):331-6. http://dx.doi.org/10.1016/j.drudis.2012.11.011

p

1 - p

β

1

1-β1

1-α1

α

1

β

2

1-β2

C 2

C 2

C 2

C 2

C 0

C 1

C 1

C 0

C 1

C 1

1-αi

αi C i

C i

C i

C i

β

i

1-βi

1-α2

α

2

Stage i=0 Stage i=1 Stage i=2.... ...Stage i=m

.......

.......

a

b

c

d

• Example

Torching the Haystack

Time

New 2 2 2 + 2 = 4

Old 1 5 1 + 5 = 6

Lendrem DW More haste, less development speed. Scrip Magazine. Dec 1995, 22-23.

• Example

If p=0.10 then the average number of drugs tested before the first success = 1/p = 10

So the average time to launch the first drug:

= (10 x 1) + 5 = 15 years

= (10 x 2) + 2 = 22 years

Torching the Haystack

New

Old

New 2 2 2 + 2 = 4

Old 1 5 1 + 5 = 6

Lendrem DW More haste, less development speed. Scrip Magazine. Dec 1995, 22-23.

Torching the Haystack

• Conclusion?• For high risk projects, the expected time to market is

actually SHORTER for the serial process EVEN THOUGH THE CYCLE TIME is LONGER.

• This is the Development Speed Paradox

Lendrem DW, Lendrem BC The Development Speed Paradox: Can increasing development speed reduce R&D productivity? Drug Discov Today. 2014 http://dx.doi.org/10.1016/j.drudis.2013.09.002

The faster you go the longer it takes.

# screened = 38# discovered = 3# launched = 3

# screened = 58# discovered = 5# launched = 4

10

20

30

40

50

10

20

30

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

Cycle Time = 2+2 = 4 yrs Cycle Time = 1+5 = 6 yrs

Years

The Tetris Model

Torching the Haystack• By placing tasks in parallel to reduce cycle time we

inadvertently:• Increased R&D costs• Increased late-stage attrition rates• Increased expected time to market

• As a result, the industry became really slick at delivering late-stage failures to the market place, precipitating the current R&D productivity crisis.

Lendrem DW, Lendrem BC Torching the Haystack: Modelling fast-fail strategies in drug development. Drug Discov Today. 2013 Apr;18(7-8):331-6. http://dx.doi.org/10.1016/j.drudis.2012.11.011

Torching the Haystack

• The M25 Effect• Reducing Development Speed may actually increase

R&D throughput. • After London’s major orbital motorway where speed

limits were first reduced in the UK in order to increase traffic throughput.

Lendrem DW, Lendrem BC The Development Speed Paradox: Can increasing development speed reduce R&D productivity? Drug Discov Today. 2014 http://dx.doi.org/10.1016/j.drudis.2013.09.002

Torching the Haystack

Looking for a needle in a haystack?• Get the science right. Build opportunities to kill

molecules earlier in the development cycle.

• Assays that prevent molecules from entering the development process.

• Assays that allow elimination of molecules early in the development process.

Torching the Haystack

• Thanks• Richard Peck (Lilly)• Fred Snikeris (Quintiles)• Stephen Senn (CRP-Sante)• Clare Lendrem (NCL)• Frank Bonner (NCL)• Wan-Fai Ng (NCL)• John Isaacs (NCL)• MRG