The document discusses the need to organize pharmaceutical research and development differently by merging the strengths of academic and industrial drug research. It proposes creating a "Center for Open Innovation in Drug Discovery" (COIDD) to bring dedicated medicinal chemistry expertise to biological targets being studied in academia. Successful precedents for this type of center exist abroad, like the Vanderbilt Center for Neuroscience Drug Discovery, and it could place Radboud University at the forefront of translational medicine by advancing promising scientific discoveries toward clinical studies. The feasibility study would determine the focus, identify partners, and develop a business plan for creating a sustainable pharmaceutical research ecosystem through the COIDD.

1. Open Innovation in Small Molecule Lead Discovery
“Center for Open Innovation in Drug Discovery”
From Molecules to Business –25 September 2014
JacWijkmans

2. Take Home Messages
Great need to organize pharma R&D in a different way
Academia hold the key to bridge the innovation gap between exploratory research & early clinical development
Merge the strengths of academic & industrial drug research
Initiated a feasibility study to create “Center of Open Innovation in Drug Discovery” to place RU/Radboudumcat forefront of translational medicine
Similar successful initiatives exist abroad that have proven to provide a sustainable academic drug discovery enterprise

3. The Pharma Landscape
Society
‒Increasing incidence of chronic diseases.
‒Escalating health care costs
‒Increased patient awareness
‒Personalized health care
Industry
‒Declining productivity
‒Risk aversion
‒R&D externalization
‒Late stage focus
‒Innovationpull
‒Driver: Shareholder value
Academia
‒Austerity measures
‒Clinical trial experts
‒Increasingly entrepreneurial
‒Early stage focus
‒Valorizationpush
‒Driver: Publications & health

4. Evolving R&D Process
<2005: The ‘good old days’
2005 -present:Shift fromR&D toS&D (Search & Development)
Industry
Academia
Pre-clinical candidate

5. Need to Organize Early R&D Differently
Spin-off
CRO #1
CRO #2
CRO #3
?
A:
B:
‒Too early to out-license
‒Shortagein funds
‒Missing skills
‒No open innovation(recycling of knowledge, molecules, IP)
Issues

6. Academia Hold the Key, however, …
… while targets, assays, compound synthesis & patients are present, medicinal chemistry capabilities are critically missing
Frye et al. Nature Rev. Drug Discov. 10, 2011, 409

7. Medicinal Chemistry
Optimizing Molecular properties to get into Business
Not acceptable Ideal
1. Affinity
2. Selectivity
3. Efficacy
4. Solubility
5. Metabolic Stability
6. Protein binding
7. Toxicity

8. Medicinal Chemistry
Optimizing Molecularpropertiestoget intoBusiness
Ideal
Not acceptable
1. Affinity
2. Selectivity
3. Efficacy
4. Solubility
5. Metabolic Stability
6. Protein binding
7. Toxicity
Multidimensional
optimization
paradigm

9. Empower Academic Drug Research
Academic biomedical research
Medicinal chemistry capabilities
“Blend academic biomedical research with industry- standard drug discovery capabilities to valorize innovation”
“Establish a leading force in academic drug discovery”
Center for Open Innovation in Drug Discovery
COIDD

10. Creating Value Chains

11. A Sustainable Pharma R&D Ecosystem
IP
(pre-)clinical candidates
Platform technologies
Spin-offs
Publications
Synergies/cross- overs
Education & training
$$$
$$$
Potential projects identified
European Lead Factory
HTS

12. Center forOpen Innovationin Drug Discovery (COIDD)
Incorporate the highest level of drug discovery into academic research and advance the most exciting scientific breakthroughs towards the development of drug candidates suited for clinical studies
Vision
Establish an unique & sustainable pharmaceutical R&D ecosystem to create new small molecule therapeutics to improve public health and place RU/Radboudumcat forefront of translational medicine
Mission

13. COIDD CoreExpertise
MedicinalChemistry
Chemical Biology
Drug discovery
Tool compounds
Project Management & Development
Leads & (pre)clinicalcandidates
New projects
industry-trained professionals
Dedicated facilities

14. Open Innovation in Practice
New molecular target or differentiating assay
Clinical
Need?
amenable
for HTS?
HTS & compound optimization
Pre-clinical candidate
out-
licensing/
partnership
For example:
Revolving funds

15. A Validated & Sustainable Model!
“De-risking investments in new treatments for brain disorders by blending academic based research with state-of- the-art drug discovery resources”
“Bringing dedicated medicinal chemistry expertise to bear on biological targets being investigated by UNC faculty”

16. A Validated & Sustainable Model!
Vanderbilt Center for Neuroscience Drug Discovery
Founded in 2003, Track Record:
2009:Drug discovery pact with J&J
2010:Research collaboration with Seaside Therapeutics
2011:Partnership Michael J. Fox Foundation
2011:License deal KarunaPharma
2012:BMS Parkinson R&D collaboration
2013:Licensing & research deal with AstraZeneca
“De-risking investments in new treatments for brain disorders by blending academic based research with state-of- the-art drug discovery resources”

17. A Validated & Sustainable Model!
“Exploiting and transforming innovative research into pharmaceutical applications in close cooperation with academic partners”
Lead Discovery Centre Dortmund
Founded in 2007, Track Record:
2011:First LDC lead licensed to Bayer
2013:2nd LDC lead licensed to Qurient
Drug discovery alliance AstraZeneca
Strategic partnership Merck Serono
2014:Drug discovery alliance Daiichi Sankyo

18. Embedding in Health Valley Region
Radboud NanomedicineAlliance
“HealthyBrain”
Technology centers

19. Feasibility Study –Next Steps
1.Get buy in and commitment from major stakeholders
2.Determine focus, identify key partners, select projects
3.Learn from “best practices”
4.Further develop business plan (revenue model, financial requirements, organization, team)
5.Apply for grants, raise capital investments
6.Build team
3Q4Q1Q2Q3Q
2015
2014
preparation phase
financing phase
Go/NoGo
Accelerate
Project X
Project Y
Start

20. Conclusions
Great need to organize pharma R&D in a different way
Academia hold the key to bridge the innovation gap between exploratory research & early clinical development
Merge the strengths of academic & industrial drug research
The COIDD will place RU/Radboudumcat forefront of translational medicine
Successful & sustainable precedents of COIDD exist but The Netherlands are falling behind … and we are determined to change this!

21. Initiators
Prof. Floris Rutjes
Dr. Thea van Kemenade
Prof. Alain van Gool
Dr. Pedro Hermkens
Dr. JacWijkmans