Significant unmet medical needs in both large and orphan indications make autoimmunity and inflammation an attractive field of research for industry companies. Scientists are striving to identify novel targets and mechanisms of action, and to apply exciting new product platforms and technologies in this space. But major challenges remain in demonstrating improved efficacy over established standards of care, identifying quality preclinical research models and stratifying patient populations to improve response rates. Drug Discovery for Autoimmunity and Inflammation explores the application of new science and technology in the development of a next generation of safe and effective therapeutics in this important therapeutic area.
Final Agenda
Recommended Short Courses*
SC2: Translational Considerations for Development of Monoclonal Antibodies Part I: Focus on Early Discovery - Detailed Agenda
SC7: Translational Considerations for Development of Monoclonal Antibodies Part II: Focus on Nonclinical Development to the Clinic - Detailed Agenda
*Separate registration required
MONDAY, MAY 1
7:00 am Registration and Morning Coffee
8:30 Chairperson’s Remarks
Rajita Pappu, Ph.D., Senior Scientist, Genentech
8:40 Targets and Pathways for Airway Diseases
Matthew Sleeman, Ph.D., Executive Director, Immunology & Inflammation, Regeneron Pharmaceuticals, Inc.
In this talk I will present an overview of pathways and the new targets that are being considered in respiratory disease and the underlying data that supports these mechanisms; in addition I will discuss how translational medicine is being used to find biomarkers to improve response rates and how newly described phenotypes of airway disease such as ACOS (asthma COPD overlap syndrome) are being used to develop new biological therapies.
9:10 IL33 in Lung Inflammation
Rajita Pappu, Ph.D., Senior Scientist, Genentech
Dysregulated Type-2 inflammation is associated with a number of allergic and atopic diseases. The significance of Type-2 cytokines, IgE and eosinophils in disease pathophysiology is most appreciated in asthma, where many trials have demonstrated clinical benefit from blocking Type-2 cytokines. We demonstrate IL33 regulates multiple pathogenic pathways including IL5 and IL13. These data suggest blocking IL33 signaling in asthma may provide clinical benefit due to inhibition of multiple pathogenic pathways.
9:40 KEYNOTE PRESENTATION: Opportunities and Challenges for Biotherapeutics in Autoimmunity and Inflammation
Christian Antoni, Ph.D., Vice President, Immunology & Inflammation, Sanofi
Biotherapeutics have revolutionized the treatment outcome for major autoimmune diseases and greatly enhanced our understanding of the underlying immune-pathology but rarely achieved complete disease control. We have now the opportunity to apply the knowledge gained to further improve treatment outcomes by tackling efficacy ceilings and to expand into underserved smaller indications while facing challenges of biosimilar entry, high CMC costs and the need to demonstrate added value for new drugs.
10:10 Coffee Break
10:45 Chairperson’s Remarks
10:50New Targets and Pathways to Treat Unmet Medical Need in Scleroderma and Fibrotic Diseases
Elma Kurtagic, Ph.D., Principal Scientist, Momenta Pharmaceuticals
Development of novel therapeutics is confounded by our inability to understand the complex basis of disease, resulting in a high failure rate in development and unclear benefit for patients. We developed high-resolution analytics to identify drug targets and patient stratification markers that address unmet medical need in autoimmune disease. This presentation will describe the application of this technology to RA and Scleroderma.
11:20 Antibodies Specific to Damaged Arthritic Cartilage as Imaging Probes and for Targeting Payload Drugs to Joint with Rheumatoid Arthritis and Osteoarthritis
Ahuva Nissim, Ph.D., Associate Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London
We have developed a panel of human scFvs that bind specifically to collagen type II post-translationally modified by oxidants present in arthritic joints, anti-ROS-CII: a) bind specifically to human rheumatoid arthritic and osteoarthritic cartilage and to cartilage from murine models of inflammatory arthritis and osteoarthritis; b) enhance resolution of inflammation by targeting payload drugs specifically to inflamed arthritic joints; and c) detect disease activity in osteoarthritic joints before any overt cartilage damage.
11:50 Old Target Revives: Potential Novel Therapeutic Strategy for Rheumatoid Arthritis
Yoshi Itoh, Ph.D., Associate Professor and Principal Investigator, Cell Migration Group, Kennedy Institute of Rheumatology, University of Oxford
Rheumatoid arthritis (RA) is characterized by destruction of joint tissues by metalloproteinases (MPs). MPs were considered to be therapeutic targets, but clinical trials of broad spectrum MP inhibitors were all failed due to lack of efficacy and side effects. However, recent studies have indicated that highly selective inhibition of some MPs may provide significant benefits in RA. Potential novel therapeutic strategies for RA will be discussed.
12:20 pm Sponsored Presentation (Opportunity Available)
12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:50 Session Break
2:20 Problem-Solving Breakout Discussions
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.
Tolerance Induction for Autoimmune Disorders
Moderator: Francisco Quintana, Ph.D. Associate Scientist, Brigham and Women’s Hospital; Associate Professor, Neurology, Harvard Medical School
- What are the available strategies for tolerance induction in autoimmune disorders?
- Do we know which antigens should we target to treat autoimmune disorders?
- In which disease should these strategies be tested first?
- Which endpoints should be analyzed?
Development of Next Generation Diagnostics and Treatment for Arthritic Conditions
Moderator: Ahuva Nissim, Ph.D., Associate Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London (Confirmed)
- What are the unmet needs of the current diagnostic and treatment?
- Systemic vs targeting treatment?
- What are the possible targets?
- What are the unmet need to define non responders?
- Why no treatment is available for osteoarthritis?
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Chairperson’s Remarks
4:10 Bicycles and Bicycle Drug Conjugates: Next Generation Therapeutics
Sir Gregory Winter, Ph.D., FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics
Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many indications, including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates™ (BDCs); a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. This presentation will describe both the Bicycle® and BDC platforms.
4:55 Young Scientist Keynote: Programming Proteins by Deep Sequencing and Design
Tim Whitehead, Ph.D., Assistant Professor, Chemical Engineering and Materials Science, Michigan State University
Next-generation sequencing has presented protein scientists with the ability to observe entire populations of molecules before, during, and after a high-throughput screen or selection for function. My group leverages this unprecedented wealth of sequence-function information to design and engineer protein affinity, specificity, and function and to infer structural complexes of proteins. My talk will present an overview of the above and detail methodological improvements that enable the engineering work.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing
6:55 End of Day
TUESDAY, MAY 2
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Remarks
Kris F. Sachsenmeier, Ph.D., Associate Director, Translational Sciences, AstraZeneca
8:30 Modulating T Cell and Myeloid Cell Functions for Treatment of Autoimmune Diseases and Cancer
Tariq Ghayur, Ph.D., Distinguished Research Fellow, AbbVie Bioresearch Center
Advances in T cell and myeloid cell biology coupled with advances in protein engineering provides novels ways to modulate immune functions for treatment of a variety of disease states. The challenges now will be to identify the right target and/or target combinations and to design the right therapeutic modalities to modulate immune functions to achieve the desired outcome.
9:00 XmAb5871, A Non-Depleting B Cell Inhibitor for the Treatment of Autoimmune Diseases
John Desjarlais, Ph.D., CSO, Xencor
FcγRIIb is an inhibitory receptor that regulates B cell responses through a negative feedback loop that requires co-localization of FcγRIIb to the BCR complex. XmAb5871 is an anti-CD19 antibody whose Fc domain was engineered to increase affinity for FcγRIIb dramatically. In vitro and in vivo studies show potent B cell suppression. Early clinical data demonstrate B cell inhibition in patients and promising activity in rheumatoid arthritis and IgG4 related disease (IgG4-RD).
9:30 Parallel Aspects of the Microenvironment in Cancer and Autoimmune Disease: Possible New Therapeutic Targets?
Miki Rahat, D.Sc., Assistant Professor, Immunology, Technion; Director, Research Laboratories, Carmel Medical Center
Cancer and autoimmune diseases are fundamentally opposite pathological conditions, as the immune response is suppressed and unable to eradicate tumor cells in the former, while it is hyper-activated against self-antigens in the latter. Nevertheless, some intriguing similarities, particularly in aspects relating to the microenvironments exist between the two. Understanding these parallels may help identify new therapeutic targets that might skew the microenvironment in the right direction to regain balance and homeostasis.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Adenosine and the Inflammatory Microenvironment: Turning the Heat Off or On?
Kris F. Sachsenmeier, Ph.D., Associate Director, Translational Sciences, AstraZeneca
We have identified that co-blockade of the ectonucleotidase that generates adenosine CD73 and the A2A adenosine receptor (A2AR) that mediates adenosine signaling in leukocytes, by using compound gene-targeted mice or therapeutics that target these molecules, limits tumor initiation, growth, and metastasis. This tumor control requires effector lymphocytes and interferon-gamma. These data are presented in light of experiments showing that adenosine also plays a role in shaping inflammation associated with autoimmunity.
11:20 Non-Antibody Based Cytokine Trapping Molecules for the Treatment of Asthma and Atopic Dermatitis
Erik Depla, Ph.D. Expert, Discovery Biology, VIB
IL-33 and TSLP are two cytokines that are released from epithelial surfaces and which control the fate of downstream allergic immune responses in asthma and atopic dermatitis. We have developed a new type of biologics that function as high affinity decoy receptors for IL-33 and TSLP. The underlying principle and data showing their potent antagonistic activity in vitro and in murine models of allergic disease will be presented.
11:50 When Is It Right, and When Is It Not Right, for Therapeutic Antibodies to Engage Fc Receptors?
Anthony Shock, Ph.D., Director, Immunology Portfolio, UCB
Direct targeting of Fc receptors (activating and inhibitory FcγRs and FcRn) is considered an attractive concept to treat autoimmune diseases and how the pharmaceutical industry is approaching this will be discussed by focusing on specific examples of biotherapeutics in clinical development. In contrast, other drugs are being developed which have been designed to avoid FcR engagement and this will also be discussed by reference to specific examples in the clinic.
12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Rachel Ettinger, Ph.D. Senior Scientist Respiratory, Inflammatory, and Autoimmune Diseases, MedImmune
2:05 Nanoparticles for the Therapeutic Induction of Antigen-Specific Tolerance in Autoimmune Diseases
Francisco Quintana, Ph.D. Associate Scientist, Brigham and Women’s Hospital; Associate Professor, Neurology, Harvard Medical School
Here we describe nanoparticles (NPs) that co-administer the aryl hydrocarbon receptor (AhR) agonist ITE and T-cell epitopes to dendritic cells (DCs) in vivo to reestablish immune tolerance in autoimmune disorders. These NPs induce tolerogenic DCs through the AhR-dependent induction of Socs2, inhibiting nuclear factor kB (NF-kB) activation. Consequently, NP-induced tolerogenic DCs induced antigen-specific Tregs, suppressed pathogenic T cells and arrested the development of experimental autoimmunity.
2:35 Tolerogenic Immunotherapy for Autoimmune Disease Using Antigen-Encapsulating PLG Nanoparticles
Stephen D. Miller, Ph.D., Professor, Microbiology-Immunology and Dermatology, Northwestern University
We have demonstrated the utility of i.v infusion of antigen-encapsulating PLG nanoparticles (Ag-NP) for therapy of Th1/Th17-mediated autoimmune disease models of MS, T1D, and celiac disease. Ag-NP-induced tolerance is mediated by both PD-L1/PD1 anergy and Treg activation and dependent on particle uptake and antigen re-presentation by splenic marginal zone and liver APCs via the MARCO scavenger receptor. This approach is being tested in a phase 1 trial in celiac disease.
3:05 Featured Poster Presentation: Antibodies Against Ion Channel Targets for Autoimmune Disorders
Yelena Bisharyan, Ph.D., Director, External Alliances, Tetragenetics Inc.
Ion channels have been historically difficult to raise antibodies against due to sequence conservation, paucity of cell surface epitopes, and poor expression levels in heterologous systems. Tetragenetics addresses these issues by combining a technology for membrane protein expression in Tetrahymena thermophila with antibody generation in phylogenetically diverse animals to develop therapeutic antibodies against a range of ion channel targets including Kv1.3, a voltage-dependent channel produced by effector memory T-cells implicated in certain autoimmune disorders.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 Disease Heterogeneity and Drug Response Subsets in Rheumatoid Arthritis
Michael Townsend, Ph.D., Associate Director, Biomarker Discovery OMNI, Genentech
Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease and the relationship between drivers of disease in RA and therapeutic outcome is incompletely understood. Advances are needed if improved drugs are to be developed. I will discuss our work using genomics, histologic phenotyping, and cellular analysis of RA synovial samples that have revealed different pathological phenotypes of RA with differential association with disease activity, clinical progression, and response to drug therapy.
4:55 Altered B Cell Subsets in SLE
Rachel Ettinger, Ph.D. Senior Scientist Respiratory, Inflammatory, and Autoimmune Diseases, MedImmune
Here, we describe an unusual subset of B cells highly expanded in a large cohort of systemic lupus erythematosus (SLE) patients. These B cells displayed a unique phenotype not noted on other B cell populations, including high densities of CD11c, FcRL5, and T-bet. These CD11chi B cells significantly correlate with SLEDAI, autoantibodies and IL-21. CD11chi B cells may serve as an important pharmacodynamic marker in clinical trials that target inflammatory processes.
5:25 End of Drug Discovery for Autoimmunity and Inflammation
5:30 Registration for Dinner Short Courses
Recommended Dinner Short Courses*
SC13: Phenotypic Screening Applications and Technologies - Detailed Agenda
SC14: Overcoming the Challenges of Immunogenicity Assays - Detailed Agenda
*Separate registration required