Day Two

31 January, 2013

8.00 Registration, Coffee & Networking

8.55 Chair’s Opening Remarks:

Michael Lisanti, Director, Breakthrough Breast Cancer Research Unit, The University of Manchester

PRACTICAL LESSONS LEARNT FROM CANCER METABOLISM DRUGS IN THE CLINIC

9.00 Case Study: Targeting Tumor Hypoxia with TH-302 as Anti-Cancer Therapy

An introduction and overview of tumor hypoxia and the design and properties of TH-302
Pre-clinical data demonstrating its successful targeting to hypoxic niches of solid tumors
Clinical data demonstrating therapeutic benefit of TH-302 in patients with various solid tumors

Harold Selick, CEO, Threshold Pharmaceuticals

9.30 Case Study: Design of Optimized Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors

An overview of the rationale and design of potent NAMPT inhibitors.
Sharing experiences learnt from successful lead optimization

Peter Dragovich, Principal Scientist, Genentech

10.00 Roundtable Master Mind Groups. A highly effective and energising format for you to:

Access the knowledge of fellow attendees
Collaboratively predict future challenges in this space
Review key learning points and set next steps

10.30 Morning Refreshments

IDENTIFYING NOVEL TARGETS FOR IMPROVED DRUG DISCOVERY

11.00 Understanding Mechanisms that Lead to Aberrant Cell Growth and Proliferation

Revisiting the Warburg Effect and exploring our current understanding of the consequences
Discussing enhanced serine metabolism as one of these consequences of the Warburg Effect
Studying druggable phenotypes arising from altered epigenetic status of cells

Jason Locasale, Assistant Professor, Cornell University

11.30 Targeting Pancreatic Cancer using Autophagy and Metabolism

Inhibition of autophagy leads to decreased oxidative phosphorylation, a drop in ATP production, and ultimately growth inhibition of resistant pancreatic cancer
Exploring Autophagy as a key component of pancreatic cancer metabolism in multiple clinical trials assessing the efficacy of hydroxychloroquine as an autophagy inhibitor in pancreatic cancer

Alec Kimmelman, Assistant Professor, Radiation Oncology, Dana Farber Cancer Institute

12.00 Case Study: Structure-Function Studies of a Glutaminase-Inhibitor Complex

Understanding the design and rationale behind Agios’ Glutaminase-Inhibitor
Exploring full-length human glutaminase in complex with an allosteric inhibitor

Byron DeLaBarre, Associate Director, Biochemistry, Agios

12.30 Lunch

1.30 Preclinical Characterization of Antagonists of 6-Phosphofructo-2-Kinase that Suppress Glucose Metabolism and Tumor Growth

PFKFB3 is a bifunctional enzyme activated in human cancer cell lines and tumors, increased by hypoxic exposure, and required for tumorigenic growth
Potent antagonists of PFKFB3 were identified and the latest results will be presented

Gilles Tapolsky, CSO, Advanced Cancer Therapeutics

2.00 Attacking PFKFB3 Using a Structure-Based Design Approach

Biological rationale for the target in the context of metabolism and tumor micro-environment
Strategy for the structure-based design approach
Emerging understanding of how to combine the metabolic intervention with existing therapies

Lars Ährlund-Richter, CSO, Kancera

2.30 Concluding Panel Discussion

Highlighting the field’s successes over the last 12 months and the potential challenges facing the field in the future
Exploring the future for cancer metabolism and feedback and conclusions from the mastermind sessions

Harold Selick, CEO, Threshold Pharmaceuticals; Valeria Fantin, Vice President, Tumor Cell Biology, Pfizer; Paul Bingham, Vice President, Research, Cornerstone Pharmaceuticals