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TUESDAY, NOVEMBER 3
7:30 am Continental Breakfast Breakout Discussion Sessions
Attendees will join a table with their peers and a moderator to discuss some of the more poignant questions facing the industry. It is an informal yet informative format that allows attendees to learn from each other and make some new contacts. To get the most out of this interactive session and format please come prepared to: share examples from your work, vet some ideas with your peers, be a part of group interrogation and problem solving, and, most importantly, enjoy talking with GPCR-loving colleagues.
TABLE 1: GPCR Dimerization Issues
Moderator:
Graeme Milligan, Ph.D., Professor of Neuroscience and Molecular Pharmacology, University of Glasgow
How to monitor receptor co-expression in native tissues
Screening for hetero-dimer selective drugs
Heterodimer assays as an avenue for tissue selectivity
TABLE 2: Functional Selectivity Challenges for GPCR Drug Discovery
Moderator:
Michel Bouvier, Ph.D., Professor, Biochemistry, Institute for Research in Immunology and Cancer, University of Montrea
What is GPCR functional selectivity ; the different flavors of ligand-biased signaling
How to measure GPCR functional selectivity and differentiate it from assay format artefacts
How to include GPCR functional selectivity into mainstream drug discovery program
TABLE 3: Strategies for De-Orphanizing GPCRs
Moderator:
Alice (Yu) Chen, Ph.D., Group Leader, Drug Discovery, Genomics Institute, Novartis Research Foundation
How to set up an orphan receptor screening assay
Tissue extraction and fractionation
Surrogate ligand screening
TABLE 4: Developing GPCR Allosteric Modulators
Co-moderators:
Jeff Reagan, Ph.D., Scientific Director, Amgen
Vincent Mutel, Ph.D., CEO, Addex Pharmaceuticals
- HTS strategy for positive and negative allosteric modulators
- SAR support: what parameters are most useful for the optimization of allosteric modulators?
- What pharmacological models are best suited for understanding allosteric modulation?
8:30 Chairperson’s Remarks
Sandra Siehler, Ph.D., Research Investigator II, Novartis Institute for BioMedical Research
8:40 CGRP Receptor Antagonists for the Acute Treatment of Migraine
Donnette Staas, Ph.D., Senior Research Fellow, Medicinal Chemistry, Merck Research Laboratories
9:10 Optimization and Mechanism of Action Studies of Allosteric Modulators of Calcium-Regulation
Jeff Reagan, Ph.D., Scientific Director, Amgen
Calcimimetics are positive allosteric modulators at the calcium sensing receptor that are used for the treatment of secondary hyperparathyroidism. This presentation will discuss application of an operational model of allosteric agonism/modulation to aid in understanding the mechanism of action of calcimimetics. Intracellular calcium flux, inositiol phosphate accumulation and ERK phosphorylation assays will be discussed.
9:40 Networking Coffee Break in the Exhibit Hall
10:40 Case Study of Preladenant, an A2A Antagonist for the Treatment of Parkinson’s Disease
Andy Stamford, Ph.D., Director, Chemical Research, Schering Plough Research Institute
11:10 Pimavanserin: From Target to Clinic Using Sensitive, HTP and Quantitative Drug Discovery Technologies
Doug Bonhaus, Ph.D., Vice President, Biosciences, ACADIA Pharmaceuticals, Inc.
Pimavanserin is a selective, highly potent 5-HT2A receptor inverse agonist in phase III clinical development for treatment of the psychosis associated with Parkinson’s disease. All aspects of the discovery and development of pimavanserin, from initial screening, through lead optimization and subsequent detailed pharmacological characterization of the final clinical candidate have been underpinned by ACADIA’s proprietary drug discovery technologies. In this talk we will illustrate how ACADIA uses its unique integrated drug discovery platforms to efficiently advance its drug discovery programs.
11:40 Negative Allosteric Modulation of mGluR5 in Parkinson’s Disease
Vincent Mutel, Ph.D., CEO, Addex Pharmaceuticals
Studies in rodents and primates strongly suggest that antagonism of the metabotropic glutamate receptor 5 (mGluR5) relieves levodopa induced dyskinesia (LID). Last year, the findings were confirmed in a small clinical trial in patients with PD-LID. Recently, Addex Pharmaceuticals reported data for their mGluR5 NAMs, ADX10059 and ADX48621, showing that both work to reduce haloperidol induced catalepsy in rodents. In September Addex announced that ADX10059 also demonstrated efficacy in the highly translational non-human primate MPTP model of PD-LID. Furthermore, Addex will report data that could differentiate this molecule from other mGluR5 NAM and other treatments in development for PD-LID. ADX10059, the first-in-class mGluR5 inhibitor, currently is in separate Phase IIb trials for treatment of gastroesophageal reflux disease (GERD) and as a migraine prophylaxis in patients with frequent attacks. ADX48621 completed Phase I testing earlier this year and is expected to start Phase IIa testing in PD-LID next year.
12:10 pm Discovery of GPCR Ligands for GPR3, a GPCR Modulating Amyloid Secretion in Alzheimer’s Disease
David Fischer, Ph.D., Director, Biology, Galapagos
GPR3 was identified as a novel Alzheimer’s drug target in human cells using Galapagos’ target discovery platform. Knock-out or knock-down of GPR3 prevents the accumulation of beta-amyloid. This GPCR appears to specifically modulate gamma-secretase activity on APP, but not to affect processing of Notch. We will discuss our strategy to identify small molecule inhibitors of GPR3’s activity on gamma-secretase.
12:40 Close of Conference
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For questions regarding the conference agenda and speaking opportunities, please contact:
Anjani Shah, Ph.D.
Conference Director
Cambridge Healthtech Institute
E-mail: ashah@healthtech.com
For sponsorship or exhibiting information, please contact:
Jon Stroup, Manager of Business Development
Cambridge Healthtech Institute
Phone: 781-972-5483
E-mail: jstroup@healthtech.com