DDI: Ohio State’s DrugDevelopment 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

DDI Bridges the Gap Between OSU’s Strengths in Early Discovery and Clinical Development

DDI

InvestmentReturns

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We are accelerating innovative research to speed cures to cancer patients

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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

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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-RISKPROJECTS

IDENTIFY PROMISING MOLECULES &

TECHNOLOGIES

DDI

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 DIRECTEDPRINCIPALINVESTIGATOR DIRECTED

Project Team ApproachDDI implements a unique, collaborative execution strategy

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Talk to us about your drug development questions:

Email: ddi@osumc.edu

Phone: 614-685-6957

Website: cancer.osu.edu/ddi

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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 Break12:30 pm LUNCH & PANEL DISCUSSION: Career Pathways for Scientists

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 TrialsPhases

FDAReview

Scale-Upto Mfg.

Post-MktgMonitoring

3-6 Years 6-7 Years 0.5-2 Years Indefinite

IND

SUBM

ITTE

D

NDA

SUBM

ITTE

D

1 2 3

~5k–10k1

APPROVED DRUG

5250candidates

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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 TrialsPhases

FDAReview

Scale-Upto Mfg.

Post-MktgMonitoring

3-6 Years 6-7 Years 0.5-2 Years Indefinite

IND

SUBM

ITTE

D

NDA

SUBM

ITTE

D

1 2 3

~5k–10k1

APPROVED DRUG

5250candidates

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Stages of Drug Discovery and Early Development

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Research & Development Value Chain

PHASE IPRE-CLINICALCANDIDATE

LEADOPTIMIZATION

LEADIDENTIFICATION

TARGETVALIDATION

TARGETID

Stages of Drug Discovery and Early Development

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TARGET ID

Function of target and its role in disease

Research & Development Value Chain

PHASE IPRE-CLINICALCANDIDATE

LEADOPTIMIZATION

LEADIDENTIFICATION

TARGETVALIDATION

TARGETID

Stages of Drug Discovery and Early Development

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TARGET VALIDATION

Demonstrate modulation of target has therapeutic effect

Research & Development Value Chain

PHASE IPRE-CLINICALCANDIDATE

LEADOPTIMIZATION

LEADIDENTIFICATION

TARGETVALIDATION

TARGETID

9:10 am Target Validation / Biochemical and Cellular Assay Development

David Fischer, PhD Executive Director, Biology, DMPK Discovery Charles River Laboratories, Inc.

Stages of Drug Discovery and Early Development

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LEAD IDENTIFICATION

Identify drug-like lead molecule Active in validated assays Acceptable specificity and selectivity

Research & Development Value Chain

PHASE IPRE-CLINICALCANDIDATE

LEADOPTIMIZATION

LEADIDENTIFICATION

TARGETVALIDATION

TARGETID

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

Stages of Drug Discovery and Early Development

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LEAD OPTIMIZATION

Identify a candidate forIND-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-CLINICALCANDIDATE

LEADOPTIMIZATION

LEADIDENTIFICATION

TARGETVALIDATION

TARGETID

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

Stages of Drug Discovery and Early Development

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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-CLINICALCANDIDATE

LEADOPTIMIZATION

LEADIDENTIFICATION

TARGETVALIDATION

TARGETID

Stages of Drug Discovery and Early Development

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PHASE I

Human safety assessment Identify maximum tolerated dose PK PD exploratory biomarkers Preliminary activity assessment

Research & Development Value Chain

PHASE IPRE-CLINICALCANDIDATE

LEADOPTIMIZATION

LEADIDENTIFICATION

TARGETVALIDATION

TARGETID

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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 Break12:30 pm LUNCH & PANEL DISCUSSION: Career Pathways for Scientists

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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