Cambridge Healthtech Institute’s Third Annual
Anti-Inflammatories
Small Molecule Approaches
April 17-18
Day 1 | Day 2 | Download Brochure
JAK kinase inhibitors will probably be the first new class of oral anti-inflammatories on the market, with the first one likely to receive approval end of 2012. But which JAK or combinations of JAK enzymes is going to prove the best to inhibit in terms of side effects and overall risk benefit profile to patients? How are the other kinase inhibitors aimed at targeting SYK and BTK, targeted for autoimmune disease but with broader potential in diseases such as cancer, progressing?
TUESDAY, APRIL 17
7:00 am Registration and Morning Coffee
8:00 Chairperson’s Opening Remarks
Martin Braddock, Ph.D., Senior Scientist, Global Project Leadership, AstraZeneca R&D
» 8:10 KEYNOTE PRESENTATION
Immunology/Inflammation Overview – via Imaging in Vivo
Paul Garside, Ph.D., Professor, Immunology, University of Glasgow
I will discuss the application of the latest real time in vivo imaging techniques in discovery and screening of drugs for immunological disorders. I will also outline the additional requirements for this approach such as novel models of disease and methods for reporting and manipulating molecular function in real time in vivo.
|
8:50 Pre-Clinical and Clinical Profile of the Dual S1P1/S1P5 Modulator BAF312, in Development for the Treatment of Multiple Sclerosis
Barbara Nuesslein-Hildesheim, Ph.D., Director, Autoimmunity, Transplantation & Inflammation Disease Area, Novartis Institutes for BioMedical Research
We will describe how the novel S1P-receptor (a G protein-coupled receptor) modulator, BAF312 affects S1P1-mediated redistribution of lymphocyte subsets in humans and how this mode of action impacts models of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis in humans. We will explain the mechanisms underlying S1P receptor-induced transient heart rate reduction and describe assays predictive for the cardiac effects seen in humans.
9:20 Discovery and Early Clinical Development of ARRY-502 a CRTh2/DP2 Antagonist for the Treatment of Allergic Inflammation
David Chantry, Ph.D., Senior Director, Cellular and Translational Biology, Array Biopharma
Th2 cells are a T cell subset that express cytokines IL-4, IL-5 and IL-13. Targeting the Th2 pathway in allergic inflammation has recently been clinically validated by the efficacy of anti-IL13 in severe asthma. CRTh2 (also known as DP2) is a G protein-coupled receptor for prostaglandin D2 that is a key regulator of Th2 driven inflammation. We have identified ARRY-502 a potent and selective CRTh2 inhibitor with properties that are favorable for chronic use in allergic inflammation. Data will be presented on the discovery and early clinical development of ARRY-502, including PK/PD from the single and multiple ascending dose studies.
9:50 Networking Coffee Break
10:15 Dissociated Agonist of Gluco-corticoid Receptor: Pre-Clinical and Clinical Development of a Selective Glucocorticoid Anti-Inflammatory
Suvit Thaisrivongs, Ph.D., Vice President, Chemistry, Pfizer
Dissociated agonists of the glucocorticoid receptor (DAGRs) that provide clinical efficacy of the commonly prescribed glucocorticoid receptor (GR) agonists but are dissociated in terms of GR-mediated side effects could represent a significant therapeutic improvement over standard glucocorticoids (GCs). PF-04171327, from a lead optimization research effort, was identified as having the differentiated profiles of DAGR in pre-clinical biomarkers for efficacy and side effects. The dissociation profiles were further evaluated clinically based on surrogate biomarkers for anti-inflammatory activity but with, for example, reduced inhibition of bone formation.
10:45 The Role of the Inflammatory Enzyme C2GNT in Diabetic Retinopathy: Journey from Lab to Clinical Application
Rakesh Chibber, Ph.D., Senior Lecturer, Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter and Plymouth
Our research group has identified C2GNT as novel therapeutic target for the treatment of chronic inflammatory conditions including diabetic retinopathy, multiple sclerosis, atherosclerosis and rheumatoid arthritis. We recently discovered and structurally identified a specific C2GNT inhibitor from a plant biomass in collaboration with British Technology International (BTGplc; http://www.btgplc.com/). This talk will cover the development of C2GNT inhibitor, MST-001.
11:15 Sponsored Presentation (Opportunity Available)
11:30 Talk Title to be Announced
Anne Fourie, Ph.D., Director, Immunology, Johnson & Johnson
12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:00 Session Break
1:25 Chairperson’s Remarks
Rajinder Singh, Ph.D., Vice President, Medicinal Chemistry, Rigel Pharmaceuticals
1:30 Discovery and Development Update on Tofacitinib
Mark Flanagan, Ph.D., Senior Principal Scientist, Worldwide Medicinal Chemistry, Pfizer
This talk will summarize the SAR developments that led to the discovery of the JAK inhibitor tofacitinib. Also provided will be clinical updates for tofacitinib in several autoimmune indications.
2:00 Development of JAK inhibitor, AC430, for Inflammation-Related Conditions
Robert C. Armstrong, Ph.D., Executive Director of Pharmacology, Ambit Biosciences Corporation
Janus kinase’s (JAK’s) are a family of receptor-associated tyrosine kinases that mediate signaling in myeloproliferative neoplasms (MPNs), other hematological malignancies and inflammatory diseases. Ambit Biosciences has engaged in the discovery and development of a selective small molecule JAK2 inhibitor with a focus on the treatment of inflammatory disease. The discovery and early development of the lead molecule AC430 will be discussed.
2:30 Discovery of a Potent Syk Kinase Inhibitor R343 as a Treatment for Allergic Asthma
Esteban Masuda, Ph.D., Vice President, Immunology, Rigel Pharmaceuticals
Syk kinase is a key regulator of the FceR1signaling pathway in mast cells. Human mast cells were used in functional cell-based assays for optimization of potent Syk inhibitor R343. R343 blocks mediators such as leukotriene and cytokine release from human mast cells and shows efficacy in allergic inflammation in the respiratory tract. R343 has shown efficacy in several animal models of asthma and advanced to Phase 1 studies in humans.
Sponsored by
3:00 Selection of Safer and More Effective Anti-Inflammatory Kinase Inhibitors Using a Platform of Primary Human Cell Based Disease Models (BioMAP® systems)
Ellen Berg, Ph.D., GM and CSO, BioSeek, LLC
The BioMAP® platform of primary human cell based disease models can discriminate standard of care and experimental anti-inflammatory therapeutics. Benchmarking experimental small molecule therapeutics (targeting PI-3K, BTK and other kinases) to standard of care therapeutics such as methotrexate, TNF-alpha antagonists, IL-1RA and JAK kinase inhibitors (CP-690,550 and INCB18424), reveals new criteria, including selectivity requirements, for selection of safer and more efficacious drug candidates.
3:15 Networking Refreshment Break in Exhibit Hall with Poster Viewing
4:00 Discovery and Development of Novel Small Molecule Inhibitors of HDAC and PI3K Isoforms for the Treatment of Immune-Inflammatory Disease
Stephen Shuttleworth, Ph.D., CSO, Karus Therapeutics
4:30 Panel Discussion: Stargazing? Progress in Probing Inflammation Early
Moderator: Martin Braddock, Ph.D., Senior Scientist, Global Project Leadership, AstraZeneca R&D
5:00 Presentation to be Announced
5:30 Networking Reception in Exhibit Hall, Poster Viewing
6:30 End of Day
Day 1 | Day 2 | Download Brochure