Intro to Ohio State's Drug Development Bootcamp

1. DDI: Ohio State’s Drug
Development Institute
Accelerating Innovative Research to Speed Cures to Cancer Patients
The Ohio State University Comprehensive Cancer Center –
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
(OSUCCC – James)
Drug Development Bootcamp: Practical aspects of
positioning your research

2. DDI Bridges the Gap Between OSU’s Strengths
in Early Discovery and Clinical Development
DDI
Investment
Returns
2
We are accelerating innovative research
to speed cures to cancer patients

3. 3
DDI Team
Erandi De Silva, PhD
 Director of Biology
 Molecular biologist with experience
in genomics, genetics and target
discovery
 Previously at Genentech
Chad Bennett, PhD
 Director of Chemistry
 Organic chemist with experience in
synthesis, medicinal and process
chemistry
 Previously at Merck & Schering-Plough
Larry Schaaf, PhD
 Director of Strategic Alliances
 Clinical pharmacologist with experience in
oncology discovery and clinical trials
 Previously at Upjohn, Pharmacia & Pfizer
 Diverse Industry Experience
 Molecular Biology
 Medicinal and Process
Chemistry
 Clinical Pharmacology
 Phase I-IV Clinical Trials
 Proven track record of
progressing therapies through
the pipeline
 Milestone based project
management approach
Jeffrey Patrick, PharmD
 Director
 Clinical scientist with experience in
preclinical and clinical development
 Previously at Dyax Corp., Mallinckrodt,
and New Haven Pharmaceuticals

4. 4
What We Do & How We Do It
 Identify partners
 Deal negotiation
 Generate money
to fuel new research
PARTNER
 Scientific rationale
 Unmet medical need
 Commercial viability
 Intellectual property
 Strategic investments
 Milestone focused
 Efficient management
 Advance projects quickly
DE-RISK
PROJECTS
IDENTIFY PROMISING
MOLECULES &
TECHNOLOGIES
DDI

5.  Coordinate project teams:
• Independent labs
• OSU shared resources
• External resources
 Facilitate access to experts
inside and outside Ohio State
 Lead independent validation
studies
 Manage external & internal
relationships
 Leverage principal
investigator’s expertise to
advance research
 Lead key studies
 Target validation
 Proof-of-concept
 Assay development
 Design new molecules
DDI PROJECT PLAN ACTIVITY
DDI DIRECTEDPRINCIPAL
INVESTIGATOR DIRECTED
Project Team Approach
DDI implements a unique, collaborative execution strategy
5

6. Talk to us about your drug
development questions:
Email: ddi@osumc.edu
Phone: 614-685-6957
Website: cancer.osu.edu/ddi
6

7. 7
AGENDA
Drug Development “Boot Camp”: Practical Aspects of Positioning Your
Research
9:00 am Welcome and Introduction
Erandi De Silva, PhD Director of Biology, OSUCCC – James Drug Development Institute
9:10 am Target Validation / Biochemical and Cellular Assay Development
David Fischer, PhD Executive Director, Biology, DMPK Discovery Charles River
Laboratories, Inc.
10:05 am Case Study: Difference Between Tool Compound and Clinical Candidate
Joe Cornicelli, PhD Director, Inflammation and Cardiovascular Pharmacology, Discovery
Research Services Charles River
11:00 am Break
11:15 am Early in vivo Safety Toxicology Considerations
Brian Roche, PhD Director, Safety Pharmacology Charles River
11:30 am Cell-Based Ion Channel and Cardiac Safety Assays
Jim Kramer, PhD Principal Scientist, Early Discovery Services Charles River
11:45 am In vitro ADMET Considerations for Drug Discovery and Lead Generation
Adrian Sheldon, PhD Associate Director of In Vitro ADMET Charles River
12:10 pm Break
12:30 pm LUNCH & PANEL DISCUSSION: Career Pathways for Scientists

8. The roadmap to an approved drug
Sources: Drug Discovery and Development: Understanding the R&D Process, www.innovation.org; CBO,
Research and Development in the Pharmaceutical Industry, 2006. PR Tufts CSDD 2014 Cost Study, Nov. 18, 2014.
Discovery Preclinical Clinical Trials
Phases
FDA
Review
Scale-Up
to Mfg.
Post-Mktg
Monitoring
3-6 Years 6-7 Years 0.5-2 Years Indefinite
INDSUBMITTED
NDASUBMITTED
1 2 3
~5k–10k
1
APPROVED
DRUG
5250
candidates
8

9. The roadmap to an approved drug
Sources: Drug Discovery and Development: Understanding the R&D Process, www.innovation.org; CBO,
Research and Development in the Pharmaceutical Industry, 2006. PR Tufts CSDD 2014 Cost Study, Nov. 18, 2014.
Discovery Preclinical Clinical Trials
Phases
FDA
Review
Scale-Up
to Mfg.
Post-Mktg
Monitoring
3-6 Years 6-7 Years 0.5-2 Years Indefinite
INDSUBMITTED
NDASUBMITTED
1 2 3
~5k–10k
1
APPROVED
DRUG
5250
candidates
9

10. Stages of Drug Discovery and Early Development
10
Research & Development Value Chain
PHASE IPRE-CLINICAL
CANDIDATE
LEAD
OPTIMIZATION
LEAD
IDENTIFICATION
TARGET
VALIDATION
TARGET
ID

11. Stages of Drug Discovery and Early Development
11
TARGET ID
Function of target and its role in disease
Research & Development Value Chain
PHASE IPRE-CLINICAL
CANDIDATE
LEAD
OPTIMIZATION
LEAD
IDENTIFICATION
TARGET
VALIDATION
TARGET
ID

12. Stages of Drug Discovery and Early Development
12
TARGET VALIDATION
Demonstrate modulation of target has
therapeutic effect
Research & Development Value Chain
PHASE IPRE-CLINICAL
CANDIDATE
LEAD
OPTIMIZATION
LEAD
IDENTIFICATION
TARGET
VALIDATION
TARGET
ID
9:10 am Target Validation / Biochemical and Cellular Assay
Development
David Fischer, PhD Executive Director, Biology, DMPK Discovery
Charles River Laboratories, Inc.

13. Stages of Drug Discovery and Early Development
13
LEAD IDENTIFICATION
Identify drug-like lead molecule
 Active in validated assays
 Acceptable specificity and selectivity
Research & Development Value Chain
PHASE IPRE-CLINICAL
CANDIDATE
LEAD
OPTIMIZATION
LEAD
IDENTIFICATION
TARGET
VALIDATION
TARGET
ID
10:05 am Case Study: Difference Between Tool Compound and Clinical
Candidate
Joe Cornicelli, PhD Director, Inflammation and Cardiovascular
Pharmacology, Discovery Research Services Charles River

14. Stages of Drug Discovery and Early Development
14
LEAD OPTIMIZATION
Identify a candidate for
IND-enabling studies
 SAR defined
 Acceptable PK
 Druggability
(permeability, metabolism, etc.)
 In vivo efficacy
 Pilot toxicology & safety
 Scale up feasibility
Research & Development Value Chain
PHASE IPRE-CLINICAL
CANDIDATE
LEAD
OPTIMIZATION
LEAD
IDENTIFICATION
TARGET
VALIDATION
TARGET
ID
11:15 am Early in vivo Safety Toxicology Considerations
Brian Roche, PhD Director, Safety Pharmacology Charles River
11:30 am Cell-Based Ion Channel and Cardiac Safety Assays
Jim Kramer, PhD Principal Scientist, Early Discovery Services Charles River
11:45 am In vitro ADMET Considerations for Drug Discovery and Lead Generation
Adrian Sheldon, PhD Associate Director of In Vitro ADMET Charles River

15. Stages of Drug Discovery and Early Development
15
PRE-CLINICAL CANDIDATE
Conduct IND-enabling studies
 Acceptable PK
 Acceptable safety margin & profile
 Feasibility of GMP manufacture
 Pre-IND Meeting
 Submit IND
Pharmaceutical Development Value Chain
PHASE IPRE-CLINICAL
CANDIDATE
LEAD
OPTIMIZATION
LEAD
IDENTIFICATION
TARGET
VALIDATION
TARGET
ID

16. Stages of Drug Discovery and Early Development
16
PHASE I
Human safety assessment
 Identify maximum tolerated dose
 PK
 PD exploratory biomarkers
 Preliminary activity assessment
Research & Development Value Chain
PHASE IPRE-CLINICAL
CANDIDATE
LEAD
OPTIMIZATION
LEAD
IDENTIFICATION
TARGET
VALIDATION
TARGET
ID

17. 17
AGENDA
Drug Development “Boot Camp”: Practical Aspects of Positioning Your
Research
9:00 am Welcome and Introduction
Erandi De Silva, PhD Director of Biology, OSUCCC – James Drug Development Institute
9:10 am Target Validation / Biochemical and Cellular Assay Development
David Fischer, PhD Executive Director, Biology, DMPK Discovery Charles River
Laboratories, Inc.
10:05 am Case Study: Difference Between Tool Compound and Clinical Candidate
Joe Cornicelli, PhD Director, Inflammation and Cardiovascular Pharmacology, Discovery
Research Services Charles River
11:00 am Break
11:15 am Early in vivo Safety Toxicology Considerations
Brian Roche, PhD Director, Safety Pharmacology Charles River
11:30 am Cell-Based Ion Channel and Cardiac Safety Assays
Jim Kramer, PhD Principal Scientist, Early Discovery Services Charles River
11:45 am In vitro ADMET Considerations for Drug Discovery and Lead Generation
Adrian Sheldon, PhD Associate Director of In Vitro ADMET Charles River
12:10 pm Break
12:30 pm LUNCH & PANEL DISCUSSION: Career Pathways for Scientists

18. 18
Panel Discussion: Career Pathways for Scientists
David Fischer, PhD Executive Director, Biology, DMPK Discovery
Joe Cornicelli, PhD Executive Director, Biology, DMPK Discovery
Brian Roche, PhD Director, Inflammation and Cardiovascular Pharmacology, Discovery
Research Services
Jim Kramer, PhD Director, Safety Pharmacology
Adrian Sheldon, PhD Associate Director of In Vitro ADMET
Tracey Papenfuss, DVM, PhD Veterinary Pathologist II
Tom Claggett Regional Sales Manager
Andy Vick, PhD Corporate Vice President, Safety Assessment