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TUESDAY, APRIL 27

7:00 am Registration and Morning Coffee

Targeting Kinases To Combat Inflammation

8:00 Chairperson's Opening Remarks

Michael Soth, Ph.D., Research Scientist, Discovery Chemistry, F. Hoffmann-La Roche, Inc.

8:10 Discovery of CP-690,550: A Potent and Selective JAK Inhibitor for the Treatment of Autoimmune Diseases and Renal Allograft Rejection

Mark Flanagan, Ph.D., Senior Principal Scientist, World Wide Medicinal Chemistry, Pfizer, Inc.

I will present on the medicinal chemistry approach and optimization of SAR leading to the identification of the Janus kinase inhibitor CP-690,550 citrate; a potential first in class oral treatment for rheumatoid arthritis and transplant rejection.

8:50 Development of a JAK-inhibitor for Rheumatoid Arthritis

Jordan Fridman, Ph.D., Director, Pharmacology, Incyte

 

 

 

 

 

9:20 Optimization of a Series of Tricyclic Inhibitors of 1 Kappa B Kinase Inhibitors and Efficacy in Chronic Murine Models of Arthritis 

William Pitts, Ph.D., Group Leader, Medicinal Chemistry, Bristol-Myers Squibb

This talk will describe the optimization of tricyclic inhibitors of IKK resulting in the identification of potent selective inhibitors which were advanced into chronic murine models of arthritis. The pharmacokinetics and pharmacodynamics of the response and some preliminary toxicology results will also be discussed.

9:50 Networking Coffee Break

10:15 A Novel Covalent Inhibitor of BTK Inhibits B Cell ReceptorSignaling and Demonstrates Efficacy in Rheumatoid Arthritis Models     

Juswinder Singh, Ph.D., CSO, Avila Therapeutics

This talk will provide an overview of the importance of Btk in BCR signaling and why it is an attractive target for autoimmune diseases. The presentation will also describe the discovery of a highly selective covalent inhibitor of Btk and how we have used this to validate in preclinical models the utility of Btk inhibitors for the treatment of arthritis.

10:45 Novel Small Molecule Inhibitors of BTK (Bruton’s Tyrosine Kinase)

Wei Chen, Ph.D., Scientist III, Medicinal Chemistry, Pharmacyclics

This presentation will provide an overview of PCI-32765, Pharmacyclics’ first generation BTK inhibitor which is in phase I clinical trials and give update on the second generation BTK inhibitors optimized for autoimmune and allergy indications.

11:15 Development of Small Molecule ERb-selective Agonists as Therapeutic Agents

Ethan Burstein, Ph.D., Director, Biosciences, Acadia Pharmaceuticals Inc.

 

11:30 Narrow Spectrum Inhibitors of cFMS, cKIT, and PDGFR Kinases as Therapies for Rheumatoid Arthritis and other Autoimmune Diseases

Daniel Flynn, Ph.D., President and CEO, Research & Development, Deciphera Pharmaceuticals

The effector phase of rheumatoid arthritis is mediated in large part by three kinases: 1) PDGFR 2) cFMS; and 3) cKIT. Deciphera has developed narrow spectrum inhibitors, highlighted by DP-4178, which exhibit robust in vivo potencies in models of collagen induced arthritis. Inhibition of PDGFR kinase blocks fibroblast-like synoviocyte proliferation and mediator release. Inhibition of cFMS kinase blocks synovial macrophage proliferation/mediator release and joint osteoclast-mediated articular cartilage/bone destruction. Inhibition of cKIT blocks mast cell release of histamine, RANKL, and other growth factors.

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

New Inflammation Targets And Pathways

1:25 Chairperson's Remarks

Jennifer Venable, Senior Scientist, Immunology Chemistry, Johnson & Johnson PRD

1:30 MIF: A Target for Drug Discovery in Autoimmune and Inflammatory Diseases     

Yousef Al-Abed, Ph.D., Professor and Director, Department of Medicinal Chemistry, Feinstein Institute

Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine, that has been implicated in the pathogenesis of both inflammatory and autoimmune diseases. We have identified a hydrophobic area within the quaternary structure of MIF and reasoned that molecules that targeted this site could be useful to inhibit MIF actions. We successfully designed ISO-1 as a potent MIF inhibitor activity in vitro and in vivo and now ISO-1 is being recognized as the gold standard inhibitor of MIF.

2:00 Hydrogen Sulfide-Releasing Anti-Inflammatory Drugs

John Wallace, Ph.D., CSO, Antibe Therapeutics

H2S is an important mediator of GI mucosal defence, and an endogenous anti-inflammatory agent. H2S-releasing anti-inflammatory drugs exhibit improved anti-inflammatory effects with little if any toxicity in the GI tract.

2:30 Panel Session: Drug Development Challenges in Autoimmunity/Inflammation

Moderator: Daniel Flynn, Ph.D., President and CEO, Research & Development, Deciphera Pharmaceuticals

 

Panelists:

Mark Flanagan, Ph.D., Senior Principal Scientist, World Wide Medicinal Chemistry, Pfizer, Inc.

Jordan Fridman, Ph.D., Director, Pharmacology, Incyte

William Pitts, Ph.D., Group Leader, Medicinal Chemistry, Bristol-Myers Squibb

Juswinder Singh, Ph.D., CSO, Avila Therapeutics

 

3:00 Selected Poster Presentation: Preclinical Profile of Novel CRAC Channel Inhibitors

Swaroop Vakkalanka, Ph.D., CEO, Incozen Therapeutics

3:15 Networking Refreshment Break, Poster and Exhibit Viewing

New Inflammation Targets And Pathways (Continued)

4:00 Small Molecule CRAC Channel Inhibitors for the Treatment of Autoimmune and Inflammatory Diseases     

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

CRAC channels are key components of the Ca2+ signaling pathway in immune cells and play essential roles in the adaptive immune response. Using sensitive assays based on Orai1 and STIM1, the principal molecular components of human CRAC channels, CalciMedica has discovered novel small molecules that inhibit CRAC channels with good potency and selectivity. These molecules are orally available, efficacious in the rat collagen-induced arthritis model, and have excellent potential to become drugs for treating autoimmune and inflammatory diseases.

4:30 Identification of the Bioactive Constituent and its Mechanisms of Action in Mediating the Anti-Inflammatory Effects of Black Cohosh and Related Cimicifuga

Allan SY Lau, M.D., Professor, Cytokine Biology Group and BioScreening Unit, Li Ka Shing Faculty of Medicine, University of Hong Kong

We present the underlying mechanism of the anti-inflammatory actions of Black Cohosh and its Chinese counterpart, Shengma (Cimicifuga species). We successfully isolated the compounds' key bioactive constituents and performed NMR spectroscopy to identify their molecular structures. Additionally, we defined the compounds' regulatory effects on cell signaling pathways in immune cells. Our findings establish these compounds as a promising new class of therapeutic agents.

5:00 Tetrac Acts at a Plasma Membrane Receptor to Modulate Expression of Inflammation-Related Genes

Paul Davis, M.D., Director, Signal Transduction, Ordway Research Institute; Professor of Medicine, Albany Medical College; Professor of Pharmacy, Albany College of Pharmacy and Health Sciences      

Small molecule, tetraiodothyroacetic acid (tetrac) regulates inflammation-relevant gene expression by blocking activation of cell surface hormone receptor, integrin. We report that tetrac suppresses expression of 5 of 6 differentially-regulated interleukin genes and up-regulates SOCS4, a cytokine signaling suppressor. Further, tetrac is anti-angiogenic by multiple mechanisms. Tetrac is the only single agent known that can affect both inflammation and the neo-vascularization that supports inflammation.

5:30 Networking Cocktail Reception in the Exhibit Hall

6:30 End of Day

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