TUESDAY, OCTOBER 5, 2010


Sponsored by
Ontario Institute Cancer Research 
7:30am Breakfast Presentation
Triphase: An Oncology Focused POC Accelerator Seeded by The Ontario Institute for Cancer Research and MaRS Innovation
Frank Stonebanks, Chief Commercial Officer, Ontario Institute for Cancer Research
Triphase represents a unique partnership between industry, private capital and the public sector, facilitated by the OICR and MaRS Innovation. We provide proof-of-concept funding, start-up company space, industry advisory and other resources to help companies to get from late pre-clinical to clinical proof of concept in oncology. Ontario plays a key role as it provides balance sheet stability, significant tax credits to foreign investors, recently streamlined regulations to enable direct foreign venture investment, access to a world class talent pool, and an entrepreneurial working environment in the vibrant innovation ecosystem of Toronto.

INNOVATIVE & ADAPTIVE CLINICAL TRIAL DESIGN

8:30 Chairperson’s Remarks

Terri Roberson, MT (ASCP), M.B.A., Sr. Director, Operations, Global External Research and Development, Lilly Research Laboratories, Eli Lilly and Company

8:40 Bayesian Approaches to POC

Donald Berry, Ph.D., Head, Division of Quantitative Sciences, MD Anderson Cancer Center, University of Texas

The sorry performance of drugs in phase 3 is due in large part to inadequate understanding of the role of the drug’s mechanism of action and that role in effecting clinical outcome. The Bayesian adaptive approach can help in building designs of early-phase clinical trials that improve this understanding. Modeling the drug’s action and the consequent clinical effects should be standard in drug development. Updating these models via the Bayesian approach using accumulating data in a clinical trial has the potential for speeding drug development, and for abandoning ineffective drugs as early as possible.

9:10 Optimization of Phase Ib/IIa Proof-of-Concept Trials

Laura Vessey, Associate Director, Global Trial Management (GTM), Early Stage Development, Global Clinical Trial Operations (GCTO), Merck Research Laboratories

This discussion will focus on the strategic and operational aspects of current state hurdles, pain points, and constraints to be addressed in determining how best to optimize a Proof of Concept trial. The challenges and opportunities that are presented to early POC clinical development are complex. These issues require proactive, creative, and cross functional problem solving skills to properly address all POC paradigms.

9:40 Therapeutic Vaccines: Advances in Understanding of Appropriate Patient Selection and Trial Design

James L. Gulley, M.D., Ph.D., F.A.C.P., Director, Clinical Trials Group, Laboratory of Tumor Immunology and Biology & Senior Clinician, Medical Oncology Branch Center for Cancer Research, National Cancer Institute National Institutes of Health

Recent clinical data has demonstrated that therapeutic vaccines can lead to improvement in overall survival for patients with metastatic castration resistant prostate cancer treated with vaccine compared with placebo without improvement in progression free survival. These positive studies raise provocative questions about therapeutic vaccines for cancer patients largely about appropriate endpoints as well as appropriate patient populations. The implications of these data for future design of therapeutic vaccine clinical trials are substantial and will be discussed

10:10 Network Refreshment Break with Poster and Exhibit Viewing

PRECLINICAL & EARLY DEVELOPMENT TO REDUCE ATTRITION

10:50 An Introduction to Reducing Attrition

Kenneth A. Savin, Ph.D., Advisor to Special Projects, Global External Research and Development/ Due Diligence, Eli Lilly and Co.

Risk, Uncertainty and Attrition are permanent attributes of Drug Discovery in the pharmaceutical industry. The way we understand and deal with these aspects of projects and programs has shaped the pharmaceutical industry and will determine our long term success. Ways of looking at and dealing with the risk, uncertainty and attrition in pre-clinical efforts will be presented.

Sponsored by
Cetero 
11:20 Combined Phase I and IIa to Accelerate Proof-of-Concept
Graham Wood, Ph.D., President, Clinical Operations - Toronto & Miami, Cetero Research
The progression from first-in-human studies to establishing proof-of-concept is a vital stage of any drug-development program. In a classic program, the move from Phase I to IIa would take a year or more. Small biotechs and large pharmaceutical companies are looking at ways to reduce the time to establish proof-of-concept. Accelerated proof-of-concept designs combine early-clinical development studies into one study with overlapping parts. Not only do the designs take the compound from Phase I to IIa in one study, but parts are run in parallel to maximize time and money savings. Case studies from two different programs will be demonstrated.
 

Sponsored by
Vince and Associates 
11:50 Luncheon Presentation
Exceeding Milestones: A Physician Perspective
Brad Vince, D.O., President & Medical Director, Vince & Associates Clinical Research

1:30pm MOA-Informed Decision Making for POC

Rumin Zhang, Ph.D., Senior Principal Scientist, New Lead Discovery, Merck Research Laboratories

We propose a Mechanism of Action (MOA)-informed decision making approach to accelerating Proof-of-Concept (POC), based on both the first principles of science and relevant historical data of drug development. MOA-informed decision making for POC begins with the selection of the best candidate that has optimal profiles of ADMETox (pharmacokinetics and toxicology) and MOA (target specificity, binding modality, kinetics and energetics) to effect the most desirable pharmacodynamics. MOA-informed decision making for POC should then include designing MOA into POC to test the initial working hypothesis about efficacy and safety. We predict that MOA is a universal catalyst for POC and a key differentiator for best in class drugs.

2:00 Clinical Proof-of-Mechanism: A meaningful Milestone in Drug Development?

Jeffrey W. Miller, M.D., Director, Exploratory Medicine, Eli Lilly & Company

Proof of concept usually requires progression to Phase II with a cumulative project cost of $25-50M. In some cases an earlier and less expensive clinical milestone may be achieved using short term biomarker response in Phase I.  The role of this earlier milestone, Proof-of-Mechanism, in guiding further Phase II investment will be discussed

2:30 Regulatory Viewpoints on Exploratory Clinical Trials (Phase 0)

Walter Janssens, Ph.D., Senior Preclinical Assessor, Preauthorisation, Coordinator Early Phase Development, Federal Agency for Medicines and Health Products

ICH M3 in its revised form addresses different possibilities to conduct exploratory clinical trials. The presentation will discuss some reasons why such trials are needed. The preclinical requirements are very important to justify parts of the protocol and some important aspects will be highlighted and different possibilities will be explained. Furthermore, implementation of GMP rules in these very early trials should be adapted to the early phase and yet be consequently applied. Experience with this type of trials in Belgium will be used to illustrate the use of such trials in practice.

3:00 Sponsored Presentation (Opportunity Available)

3:15 Networking Refreshment Break with Poster & Exhibit Viewing

PROOF-OF-CONCEPT: SCIENCE TO STRATEGY

3:45 Chairperson’s Remarks

Russell Linderman, Ph.D., Executive Director, Research Science & Technology PGRD, Pfizer Inc.

3:55 Accelerating POC – “Stairway to Heaven” or “Highway to Hell”

Joseph C. Fleishaker, Ph.D., FAAPS, FCP, VP, PGRD, St. Louis Laboratories, Clinical Research, Pfizer Inc.

Accelerating POC is not about designing a plan to get through a Phase IIa study as rapidly as possible, but is rather about collecting the key data that inform a robust POC decision in the most efficient manner. We will discuss strategic, scientific, and operational considerations of POC program design and focus particularly on areas where speed and quality must be carefully balanced.

4:25 Round Table Discussions: Defining Proof-of-Concept

What does Proof-of-Concept mean? How can a definition change how industry addresses the challenges in advancing through proof-of-concept? Join your colleagues and peers in an informal conversation to discuss how to define this development phase and does the definition help accelerate proof-of-concept.

Discussion Topics:

  • The role of the exploratory IND in APOC
  • Target validation: proof-of-concept starts in the discovery phase
  • What are the inherent problems with direct-to-patient studies?
  • Using animal models as better predictors of in-man studies
  • Business model selection to incentivize POC success

5:25 End of Conference Day