N E W S & A N A LY S I S FROM THE ANALYST’S COUCH
UK academic drug discovery Cathy Tralau-Stewart, Caroline M. R. Low and Nicola Marlin
Image courtesy of Spectral/Alamy
Pharmaceutical companies have moved away from conducting early-stage preclinical research in‑house in recent years, and are instead partnering with academic institutions to pursue programmes around emerging targets. Simultaneously, various funding organizations have invested in building drug-discovery capabilities in academic institutions. In 2011, Frye et al. published an analysis of US academic centres for small-molecule drug discovery1. No equivalent data were available for the United Kingdom, and so we carried out a survey of UK academic and non-profit organizations involved in small-molecule and/or biologic drug discovery research (see Supplementary information S1 (box) for the survey itself and Supplementary information S2 (box) for details and further analysis). We tried to achieve full coverage of UK institutes and received 38 responses, but we appreciate that not all groups were reached, and so this survey should be viewed as a snapshot of the UK academic environment in early 2013. We compared our findings with those from
Traditional academic goals such as publications and training were the highest priority for UK academics (Supplementary information S2 (box); figure 13) followed by taking new agents into the clinic and creating intellectual property, which are now included in the Research Excellence Framework (REF) evaluation of the performance of UK academic institutions.
a 9 7
Diabetes, endocrine and metabolism Gastrointestinal NA diseases Dermatology NA Orphan diseases 1 Obstetrics and NA gynaecology 0 1 0
b
4
5
3 3
9 12 11
Kinases
7 7 7
2 Ion channels 3
7
40
28 30
17 21
9
5
10
20
30
40
9
Pharmaceutical industry US academics UK academics
10
15
Proportion of projects (%)
20
Unspecified
2 0
10
20
30
40
e
21
28
20 20 13 45
9 10 10
Targets progressed to preclinical candidate stage Compounds licensed to industry Compounds/biologics reached investigational new drug status
46 43.9 33
45.1
14 9.8
Drugs approved by 7 the FDA or EMA 1.2 20
30
40
Proportion of projects (%)
Figure 1 | Drug discovery research in UK academic groups compared with US academic groups and the pharmaceutical industry. a | Research effort (%) by therapeutic area. b | Research effort (%) for individual drug targets. c | Hit identification strategies used in academic groups.
7 7 4
50
28
3
Fragment-based screening High-throughput screening
35
18
8
Undisclosed
Phenotypic NA screening Computational design Focused set screening
8
27
Repurposing NA
c
10
48 46
New targets generated in own institute Targets with significant preclinical evidence Clinically validated targets
7
0
7
5
5
15
Receptors
17
53
33
Other enzymes
Research focus and approach. Cancer, infectious diseases and neurology represent the main focus of research for both academic institutes and industry. The range of therapeutic areas addressed is similar for UK and US research (FIG. 1a). Notable exceptions are significant effort by UK groups in gastrointestinal and respiratory diseases (not separately documented in REF. 1), and a reduced effort in orphan diseases. Areas of opportunity for publicly funded research that are not a major focus of industry pipelines include diseases that affect less developed countries and orphan diseases. Many UK and US academic groups focus on unspecified targets that lie outside the traditional classes ▶ d
19
Unspecified
6
5
2
12 11 10
6
3
Ophthalmology
17 16
8
4
Survey and analysis Research structures, capabilities and aims. Most UK groups working in drug discovery are traditional academic research groups (87%) rather than dedicated centres (13%), and have been established for >7 years. The majority have 50% holding a Ph.D. Only 16% were involved in multi-university collaborations, and only 40% of research directors had >5 years of industry experience (Supplementary information S2 (box); figures 1–10). Many groups (>60%) report capabilities for generating chemical tools. However, competencies in drug metabolism, pharmacokinetics and clinical trials were uncommon, and access to high-throughput screening (HTS) facilities and associated compound libraries were not reported by any UK group (Supplementary information S2 (box); figures 11, 12). Many groups outsourced such activities. 22 21 21
Cancer Infectious diseases Cardiovascular disease Psychiatric, neurodegeneration and neurology 2 Other unclassified Stroke/neuromuscular disorders Respiratory disorders NA Diseases of less NA developed countries
the United States1, and we compared the research focus with current industry pipelines.
0
10
20
30
40
50
Proportion of projects (%)
d | Degree of target validation for projects at initiation. e | Academic drug pipelines. Sources: survey for the UK (Supplementary information S2 (box)); Nature Reviews | Drug Discovery US data normalized from REF. 1; current data from top-50 pharmaceutical company pipelines from Thomson Reuters Integrity. NA, not available.
NATURE REVIEWS | DRUG DISCOVERY
VOLUME 13 | JANUARY 2014 | 15 © 2014 Macmillan Publishers Limited. All rights reserved
N E W S & A N A LY S I S FROM THE ANALYST’S COUCH ▶ such as enzymes and receptors pursued by
industry (FIG. 1b) and small-molecule rather than biologic approaches predominate. Almost half of these innovative targets are based on new discoveries — 46% (UK) and 48% (US) — followed by drug targets with significant preclinical validation (35% (UK) and 27% (US); FIG. 1d). Strategies used to source tractable hit compounds differ considerably (FIG. 1c). US groups used HTS to a higher extent (45%) than their UK counterparts (9%), who make greater use of computational design and fragment-based screening. Funding and partnerships. Annual operating expenses for UK groups are broadly similar to US groups. Most are below £1 million (59%), with 37% within £1–10 million. Over 5 years, 63% of UK groups have raised
UK academic drug discovery Cathy Tralau-Stewart, Caroline M. R. Low and Nicola Marlin
Image courtesy of Spectral/Alamy
Pharmaceutical companies have moved away from conducting early-stage preclinical research in‑house in recent years, and are instead partnering with academic institutions to pursue programmes around emerging targets. Simultaneously, various funding organizations have invested in building drug-discovery capabilities in academic institutions. In 2011, Frye et al. published an analysis of US academic centres for small-molecule drug discovery1. No equivalent data were available for the United Kingdom, and so we carried out a survey of UK academic and non-profit organizations involved in small-molecule and/or biologic drug discovery research (see Supplementary information S1 (box) for the survey itself and Supplementary information S2 (box) for details and further analysis). We tried to achieve full coverage of UK institutes and received 38 responses, but we appreciate that not all groups were reached, and so this survey should be viewed as a snapshot of the UK academic environment in early 2013. We compared our findings with those from
Traditional academic goals such as publications and training were the highest priority for UK academics (Supplementary information S2 (box); figure 13) followed by taking new agents into the clinic and creating intellectual property, which are now included in the Research Excellence Framework (REF) evaluation of the performance of UK academic institutions.
a 9 7
Diabetes, endocrine and metabolism Gastrointestinal NA diseases Dermatology NA Orphan diseases 1 Obstetrics and NA gynaecology 0 1 0
b
4
5
3 3
9 12 11
Kinases
7 7 7
2 Ion channels 3
7
40
28 30
17 21
9
5
10
20
30
40
9
Pharmaceutical industry US academics UK academics
10
15
Proportion of projects (%)
20
Unspecified
2 0
10
20
30
40
e
21
28
20 20 13 45
9 10 10
Targets progressed to preclinical candidate stage Compounds licensed to industry Compounds/biologics reached investigational new drug status
46 43.9 33
45.1
14 9.8
Drugs approved by 7 the FDA or EMA 1.2 20
30
40
Proportion of projects (%)
Figure 1 | Drug discovery research in UK academic groups compared with US academic groups and the pharmaceutical industry. a | Research effort (%) by therapeutic area. b | Research effort (%) for individual drug targets. c | Hit identification strategies used in academic groups.
7 7 4
50
28
3
Fragment-based screening High-throughput screening
35
18
8
Undisclosed
Phenotypic NA screening Computational design Focused set screening
8
27
Repurposing NA
c
10
48 46
New targets generated in own institute Targets with significant preclinical evidence Clinically validated targets
7
0
7
5
5
15
Receptors
17
53
33
Other enzymes
Research focus and approach. Cancer, infectious diseases and neurology represent the main focus of research for both academic institutes and industry. The range of therapeutic areas addressed is similar for UK and US research (FIG. 1a). Notable exceptions are significant effort by UK groups in gastrointestinal and respiratory diseases (not separately documented in REF. 1), and a reduced effort in orphan diseases. Areas of opportunity for publicly funded research that are not a major focus of industry pipelines include diseases that affect less developed countries and orphan diseases. Many UK and US academic groups focus on unspecified targets that lie outside the traditional classes ▶ d
19
Unspecified
6
5
2
12 11 10
6
3
Ophthalmology
17 16
8
4
Survey and analysis Research structures, capabilities and aims. Most UK groups working in drug discovery are traditional academic research groups (87%) rather than dedicated centres (13%), and have been established for >7 years. The majority have 50% holding a Ph.D. Only 16% were involved in multi-university collaborations, and only 40% of research directors had >5 years of industry experience (Supplementary information S2 (box); figures 1–10). Many groups (>60%) report capabilities for generating chemical tools. However, competencies in drug metabolism, pharmacokinetics and clinical trials were uncommon, and access to high-throughput screening (HTS) facilities and associated compound libraries were not reported by any UK group (Supplementary information S2 (box); figures 11, 12). Many groups outsourced such activities. 22 21 21
Cancer Infectious diseases Cardiovascular disease Psychiatric, neurodegeneration and neurology 2 Other unclassified Stroke/neuromuscular disorders Respiratory disorders NA Diseases of less NA developed countries
the United States1, and we compared the research focus with current industry pipelines.
0
10
20
30
40
50
Proportion of projects (%)
d | Degree of target validation for projects at initiation. e | Academic drug pipelines. Sources: survey for the UK (Supplementary information S2 (box)); Nature Reviews | Drug Discovery US data normalized from REF. 1; current data from top-50 pharmaceutical company pipelines from Thomson Reuters Integrity. NA, not available.
NATURE REVIEWS | DRUG DISCOVERY
VOLUME 13 | JANUARY 2014 | 15 © 2014 Macmillan Publishers Limited. All rights reserved
N E W S & A N A LY S I S FROM THE ANALYST’S COUCH ▶ such as enzymes and receptors pursued by
industry (FIG. 1b) and small-molecule rather than biologic approaches predominate. Almost half of these innovative targets are based on new discoveries — 46% (UK) and 48% (US) — followed by drug targets with significant preclinical validation (35% (UK) and 27% (US); FIG. 1d). Strategies used to source tractable hit compounds differ considerably (FIG. 1c). US groups used HTS to a higher extent (45%) than their UK counterparts (9%), who make greater use of computational design and fragment-based screening. Funding and partnerships. Annual operating expenses for UK groups are broadly similar to US groups. Most are below £1 million (59%), with 37% within £1–10 million. Over 5 years, 63% of UK groups have raised
