Archived Content

Cambridge Healthtech Institute’s Third Annual
Small Molecule Approaches
April 17-18 

Day 1 | Day 2
Download Drug Discovery Chemistry Brochure or Anti-Inflammatories 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?


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


Immunology/Inflammation Overview – via Imaging in Vivo 

Paul Garside 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 Orally-available CRAC Channel Inhibitors for Treatment of Autoimmune and
Inflammatory Diseases

Jeffrey P. Whitten, Ph.D., Vice President, Chemistry, CalciMedica

Inhibitors of calcium-release activated calcium (CRAC) channels represent a new class of oral immunomodulatory agents with a potential safety profile suitable for chronic dosing to treat autoimmune disorders. CRAC channels, composed of Orai1 and STIM1 proteins, are exquisitely selective calcium channels and play an essential role in the adaptive immune response. CalciMedica has generated multiple structurally-distinct, potent and selective CRAC channel inhibitors that block cytokine secretion in immune cells as well as inflammation in animal models of immune disease. The lead compound is currently being tested in psoriasis patients in multiple-dose safety-studies.

11:15 Discovery and Development of Leukotriene A4 Hydrolase Inhibitors

James P. Edwards, Ph.D., Sr. Research Fellow, Immunology, Johnson & Johnson

11:45 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
BioSeek logo small
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 Principal Scientist, Global Project Leadership Development, AstraZeneca R&D

5:30 Networking Reception in Exhibit Hall, Poster Viewing

6:30 End of Day

Day 1 | Day 2
Download Drug Discovery Chemistry Brochure or Anti-Inflammatories Brochure