- 自体免疫疾病和炎症药物标靶 -
This conference focuses on small molecule and peptide or macrocyclic-based agents that have the potential to be developed into oral-based therapies for the treatment of autoimmune diseases and chronic inflammation disorders. The success of biologics for autoimmune diseases coupled with rapid advances in basic research has validated many immunology-relevant signaling pathways and uncovered new intracellular molecules to target for potential new drug agents that can enter the cell. Discovering oral-based therapies, which offer patient convenience, for autoimmune and inflammation conditions is a high priority in the drug discovery industry because of the chronic nature of many autoimmune and inflammation conditions and the fact that their incidence is predicted to steadily increase due to the growing aging population. Join CHI's Autoimmune and Inflammation Drug Targets conference to network with colleagues and stay abreast of this rapidly advancing field.
Day 1 | Day 2
Thursday, September 27
11:50 am Conference Registration Open
12:20 pm Plenary Keynote Program
2:00 Refreshment Break in the Exhibit Hall with Poster Viewing
New Intracellular Drug Targets for Inflammation
2:45 Welcome Remarks
Anjani Shah, PhD, Conference Director, Cambridge Healthtech Institute
2:50 Chairperson’s Opening Remarks
Shruti Sharma, PhD, Assistant Professor, Department of Immunology, Tufts
2:55 Discovery and Investigation of Selective Immunoproteasome Inhibitors
Michael Siu, PhD, Senior Scientist, Discovery Chemistry, Genentech, Inc.
The importance of the immunoproteasome for immune cell function has led to efforts to selectively inhibit this target to deplete pathogenic immune cells for the potential treatment of autoimmune diseases. Herein, we describe the discovery of β5i (LMP7) selective inhibitors and their effects on immune cells. These inhibitors have provided new understanding of immunoproteasome inhibition that suggests selective inhibition may have limited potential for immune cell depletion.
3:25 The Anti-inflammatory Effect of SINE (Selective Inhibitors of Nuclear Export) Compounds in the Context of IBD
Sharon Tamir, Director, Strategic Product Development, Head of Neurodegenerative and Infectious Diseases, Karyopharm Therapeutics Inc.
Karyopharm Therapeutics has developed a class of compounds known as Selective Inhibitors of Nuclear Export (SINE), which reversibly bind to and inhibit the function of nuclear export protein, exportin-1 (XPO1). In murine DSS induced colitis, longer, less inflamed colons and more normal stool consistency was observed in mice treated with SINE compound. SINE compounds demonstrate the ability to reduce chronic inflammation by multiple mechanisms including inhibiting NF-kB activity even in presence of TNF-α.
3:55 Sponsored Presentation (Opportunity Available)
4:25 Refreshment Break in the Exhibit Hall with Poster Viewing
5:00 Role of STING in Innate Immunity and Implications for Drug Discovery
Shruti Sharma, PhD, Assistant Professor, Department of Immunology, Tufts
5:30 Inhibitor of NCK, a First-in-Class TCR Signaling Adaptor for Combatting Autoimmunity
Balbino Alarcon, PhD, Professor, Center for Molecular Biology Severo Ochoa, National Research Council of Spain, Madrid
Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence (PRS) in the cytoplasmic tail of the TCR’s CD3ε subunit. We have generated an orally-available, inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation at subnanomolar concentrations. The inhibitor is not immunosuppressive and exerts a long-lasting protective effect in several models of autoimmunity even when the compound is no longer present.
6:00 Pharmacological Regulation of the Keap1-NRF2 System Unveils Mitochondrial Targeting in Inflammation
Michelangelo Campanella, PhD, PharmD, Professor and Unit Head, Mitochondrial Cell Biology and Pharmacology, Research Group RVC and University College London Consortium for Mitochondrial Research
My talk will report upon Nrf2 inducers as pharmacological tolls in mitochondrial quality control operated by targeted autophagy. It will also dwell on their targeting of mitochondrial pathways which define autoimmunity and inflammation. The presentation will therefore elaborate on the prominent in cell activity of the non-covalent Keap1-Nrf2 protein-protein interaction (PPI) inhibitor PMI, structurally distinct from the covalent Keap1 modifiers (e.g., sulforaphane) and highlight promising ligands targeting mitochondrial pathways involved in the inflammatory response.
6:30 Dinner Short Course Registration
9:30 Close of Day
Day 1 | Day 2
Friday, September 28
7:00 am Registration Open
7:30 Interactive Breakfast Breakout Discussion Groups
Grab a cup of coffee and join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are available on the conference website.
The Microbiome, Autoimmunity and Inflammation
8:30 Chairperson’s Remarks
Thomas Sundberg, PhD, Senior Research Scientist I, Center for Development of Therapeutics, Broad Institute of MIT and Harvard
8:35 KEYNOTE PRESENTATION: NOD2, Innate Immunity and the Microbiome
Catherine Grimes, PhD, Assistant Professor, Department of Chemistry and Biochemistry, University of Delaware
9:05 Reverse Translation for Therapeutic Development in the Human Microbiome
Ulrich Thienel, MD, PhD, CMO, Finch Therapeutics, Inc.
A major challenge in microbiome research is interpreting correlations observed in human cohort studies or murine models. However, with the increasing abundance of clinical interventional data from experience with fecal microbiota transplantation, there is an opportunity to develop therapeutic insights directly from clinical observations. Finch Therapeutics identifies microbial therapies by observing patterns of microbial engraftment that drive clinical responses. We plan to use the patterns to develop a new generation of rationally selected microbiota therapies for Inflammatory Bowel Disease.
9:35 Presentation to be Announced
10:05 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced
Intracellular Kinase Inhibitors for Inflammation/Autoimmunity
10:45 Considerations in the Generation of Covalent BTK Inhibitors
Noel S. Wilson, PhD, Senior Scientist II, Discovery Chemistry and Technology, AbbVie
11:15 Evobrutinib (BTK inhibitor) in Autoimmunity: Preclinical Updates
Andrew Bender, PhD, Senior Scientist, Discovery Biology, EMD Serono
11:45 Sponsored Presentation (Opportunity Available)
12:15 pm Session Break
12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Refreshment Break in the Exhibit Hall with Poster Viewing
Oral-Based Approaches for Autoimmunity
1:55 Chairperson’s Remarks
Songqing Na, PhD, Senior Scientist, Biotechnology & Autoimmunity Res-AME, Eli Lilly and Company
2:00 FEATURED PRESENTATION: PTG 200, an Oral IL23 Peptide Antagonist for Ulcerative Colitis
David Y. Liu, PhD, CSO, Protagonist Therapeutics
2:30 Targeting ROR for Psoriasis and IBD
James Zapf, PhD, CSO Visionary Pharmaceuticals
Retinoic acid receptor-related orphan receptor C2 (RORc2, RORγt, or NR1F3) is essential for producing IL-17 and related cytokines, which are important drivers of many immune diseases. We used our computational chemistry platform to discover RORγt inverse agonists (antagonists) with low molecular weights and moderate LogP values, which distinguishes our compounds. Our preclinical candidates combine good oral bioavailability, potent suppression of IL-17 in human monocytes, and efficacy in models of liver fibrosis and non-alcoholic steatohepatitis (NASH).
3:00 Identification of a First-in-Class RIP1 Kinase Inhibitor in Clinical Trials for Immuno-Inflammatory Diseases via DNA-Encoded Libraries
Philip A. Harris, PhD, Senior Scientist, Pattern Recognition Receptor DPU, GlaxoSmithKline
RIP1 kinase activity is a critical driver of cell death and pro-inflammatory cytokine production downstream of multiple signaling pathways including TNFR1. Hence RIP1 inhibitors have the potential to result in a broad therapeutic benefit in inflammatory diseases. This talk will describe the identification of a novel and selective RIP1 inhibitor series from a DNA-encoded library, and the lead optimization leading to identification of development candidate GSK2982772, now in Phase IIa clinical evaluation in psoriasis, rheumatoid arthritis and ulcerative colitis patients.
3:30 Presentation to be Announced
4:00 Close of Conference