The specificity, efficacy and safety profiles of biologics make them good candidates for the treatment of the complex array of autoimmune diseases, but challenges remain related to clinical endpoints, isolation of responder populations and how to best
develop and apply treatment combinations. Emerging genetic understandings of the mechanisms of these complex disorders are now being combined with exciting new therapeutic formats and strategies in a renewed wave of attention for the use of biotherapeutics
in this therapeutic area. Biologics for Autoimmune Diseases presents a focused meeting that will offer an exciting exploration of ways in which the industry is applying new science and technology in the development of a next generation of effective
and safe therapeutics.
MONDAY, MAY 4
7:00 am Registration and Morning Coffee
Plenary Keynote Session
8:30 Chairperson’s Opening Plenary Remarks
8:40 Cancer Stem Cells and Mechanisms of Malignant Progression
Robert A. Weinberg, Ph.D., Founding Member, Whitehead Institute for Biomedical Research; Professor, Biology, Massachusetts Institute of Technology
The cell-biological program termed the epithelial-mesenchymal transition (EMT) plays a role in conferring aggressive traits on carcinoma cells. In addition, it generates cancer stem cells (CSCs) that have the ability, following dissemination,
to serve as founders of new metastatic colonies. The relationship between these CSCs and the SCs residing in normal tissues, and the participation of the CSCs in metastatic dissemination will be described.
9:25 Building an Antibody Discovery Company in a Crowded Field – the Adimab Story
Tillman Gerngross, Ph.D., CEO, Co-Founder, Adimab
The presentation will cover the evolution of Adimab from its founding in 2007 to becoming one of the few privately held profitable biotech companies in the last decade. Industry trends and specific strategic decisions along the way will be discussed
and used to illustrate the importance of integrating finance and scientific information to build successful capital efficient biotech companies.
10:10 Coffee Break
10:45 Chairperson’s Remarks
Paul D. Rennert, Founder & Principal, SugarCone Biotech Consultants LLC
10:50 KEYNOTE PRESENTATION
The Impact of the Accelerated Medicines Program (AMP) on the Development of Biologics for Autoimmune Diseases
Michael B. Brenner, M.D., Theodore B. Bayles Professor of Medicine, Harvard Medical School; Chief, Division
of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital
A consortium of clinical, molecular and computational teams sponsored by the NIH, industry and non-profit partners are working to deconstruct inflammatory diseases (RA and SLE). To identify new biomarkers and therapeutic targets, the approach
will focus on molecular analyses in single cells and subsets from involved tissues with systems level bioinformatic analyses to reveal networks, nodes and regulators of pathways in specific cell types responsible for end organ pathology.
11:20 Unmet Medical Need in Autoimmune Diseases: Opportunities for Biotherapeutics
Roland Kolbeck, Ph.D., Senior Director, Research, Respiratory, Inflammation & Autoimmunity, MedImmune
The approval of mAbs for the treatment of autoimmune diseases has provided patients with additional options to manage their illnesses. However, a large medical need remains for additional therapies. Two examples of mAbs at various stages of clinical
testing, exemplifying potentially new therapeutic options, are discussed: sifalimumab, a monoclonal antibody inhibiting INF-α for the management of SLE and mavrilimumab, a antagonistic antibody directed against GMCSF-R for the management
11:50 Sponsored Presentation (Opportunity Available)
12:20 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own
1:20 Session Break
1:50 Chairperson’s Remarks
Paul D. Rennert, Founder & Principal, SugarCone Biotech Consultants LLC
1:55 CSF1 and IL34 Cytokines as Therapeutic Targets in Macrophage Driven Inflammation
Ali Zarrin, Ph.D., Scientist, Immunology,
We describe how neutralizing both CSF-1 and IL-34 versus single blockade affects the outcome of a variety of inflammatory diseases such as collagen-induced arthritis compared to TNF blockade. In addition, we provide mechanistic insights on how
CSF1 and/or IL34 specifically contribute to the inflammation, bone remodeling and macrophages subsets throughout the study. We propose that single and dual blockade of IL34 and CSF1 provides new therapeutic opportunities in disease indications
that involve macrophages.
2:25 Cell-Penetrating Bacterial Effector Proteins as a Novel Class of Biologic Autoimmune Therapeutics
Schmidt, Ph.D., Director & Head, Institute of Infectiology - ZMBE, University of Münster
Bacterial pathogens have developed intriguing molecular machines for injecting effector proteins into host cells to exploit, inhibit or modulate signaling pathways. We discovered that some effector proteins are cell-penetrating proteins (CPP)
that enter cells autonomously. In a paradigm change, these effectors are seen no longer as targets but rather as tools for manipulating signaling pathways for the benefit of the host (e.g. in autoimmune disorders).
2:55 Activated Invariant NKT Cells Control Central Nervous System Autoimmunity in a Mechanism that Involves Myeloid-Derived Suppressor Cells
Ph.D., Research Assistant Professor, Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine
Activation of invariant natural killer T (iNKT) cells with a canonical glycolipid antigen confers protection against central nervous system autoimmunity in mice. Mechanistically, we demonstrate that their cooperation with myeloid-derived suppressor
cells (MDSCs) in this process is critical. We propose that these immunosuppressive interactions between iNKT cells and MDSCs could be exploited for the development of improved immunotherapies for multiple sclerosis and other autoimmune diseases.
3:25 Modulation of TLRs for Potential Treatment of Rare Autoimmune Diseases
Sullivan, Ph.D., Vice President, Development Programs and Alliance Management, Idera Pharmaceuticals, Inc.
Toll-like receptors (TLRs) play a crucial role in autoimmune diseases through the detection of damage-associated molecular patterns (DAMPs) and the induction of pro-inflammatory cytokines. Blocking the activation of TLRs may provide a novel
treatment approach for rare autoimmune disease such as myositis, by preventing activation of the pro-inflammatory response, thereby cutting off the disease cycle that propagates inflammation. Clinical proof of concept of TLR antagonism
has been established in psoriasis.
3:55 Refreshment Break in the Exhibit Hall with Poster Viewing
4:35 Problem-Solving Breakout Discussions
Challenges in Designing Proof-of-Concept Studies for Experimental Therapeutics in Inflammatory Diseases
Moderator: Joseph R. Arron, M.D., Ph.D., Associate Director & Senior Scientist, Biomarker Discovery, Genentech
- Which outcome measures are most appropriate for a given mechanism of action?
- How can predictive, prognostic, and pharmacodynamic biomarkers contribute to more informative trials?
- How do we account for effects of background immunomodulatory therapies and/or past treatment failures?
- What are the tradeoffs between dose ranging and getting robust outcome data?
Blocking Costimulatory Receptors on T-Cells for Autoimmune Diseases
Moderator: Jonathan Back, Ph.D., Head of In Vivo Pharmacology, Biologics Research, Glenmark Pharmaceuticals, Switzerland
- What autoimmune /inflammatory diseases possess a recognized T-cell component?
- Costimulatory receptors on T cells: is there a consensus definition? Cytokine receptors? Integrins?
- Redundancy of these costimulatory signals
- Importance of costimulation for primary vs memory / chronic responses
- The Abatacept example: Lessons learned
Bispecific Antibodies for Autoimmune Diseases
Moderator: Matthew D. Linnik, Ph.D., Senior Research Fellow, Autoimmunity Lilly Biotechnology Center
- Is there good rationale for bispecifics?
- What are some of the best target combinations?
- How important is compatible posology and pharmacology?
- Are there ways to prospectively assess for rare safety events (serious infections, etc) in early clinical development?
- How critical are active comparators in phase 2 for decision-making?
Targeting Macrophages in Autoimmune and Inflammatory Diseases
Moderator: Ali Zarrin, Ph.D., Scientist, Immunology, Genentech
- Are we able to define and track various macrophage subsets in inflammatory diseases?
- What are the major therapeutic areas and drugs that target macrophages in inflammatory diseases?
- What are the emerging drug targets/pathways in macrophages in inflammatory diseases and cancer?
- What are the challenges with targeting macrophages in chronic inflammatory diseases?
5:35 Welcome Reception in the Exhibit Hall with Poster Viewing
6:50 End of Day
TUESDAY, MAY 5
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
Tony Manning, Ph.D., Vice President, Research, Momenta Pharmaceuticals
8:30 Targeting Mechanisms at Sites of Complement Activation for Therapeutic Applications
V. Michael Holers, M.D., Head, Division of Rheumatology, University of Colorado, Denver
Complement therapeutics are being successfully applied to a number of human orphan diseases, and these efforts will be briefly discussed. In order to optimally broaden the use of therapeutics directed to the complement system, though, it is
likely that strategies to identify novel activation mechanisms and target inhibitors to sites of complement activation must be developed. Ongoing studies addressing these strategies will be reviewed.
9:00 Dampening Pathological Immune Responses via Targeting OX40 with GBR 830, an Antagonist Monoclonal Antibody
Ph.D., Head, In Vivo Pharmacology, Biologics Research, Glenmark Pharmaceuticals
GBR 830 is a humanized anti-human OX40 monoclonal antibody that demonstrates antagonistic activity. Preclinical data have revealed that targeting OX40 with GBR 830 can potently suppress pathological T cell mediated immune responses such as
graft versus host reactions and psoriasis. These data have supported and lead to the testing of GBR 830 in the clinic.
9:30 Selective Modulation of Fc Receptors for Improved Therapy of Orphan Autoimmune Diseases: Lessons from IVIg
Tony Manning, Ph.D., Vice
President, Research, Momenta Pharmaceuticals
Based on extensive characterization of the mechanism of action of IVIg, both in animal models and in humans, we rationally designed a series of recombinant drug candidates with the potential to deliver improved therapeutic benefit compared
to IVIg. These agents are termed Selective Immunodulators of Fc Receptors (SIF’s), and they selectively modulate the activity of members of the Fcg receptor family. In cell and animal models of immune-complex-mediated autoimmunity,
SIF’s display up to 500-fold greater potency than IVIg.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Clinical Update for Secukinumab, an anti-IL-17 Antibody for Treatment of Psoriasis
Franco Di Padova,
Ph.D., Director, Novartis Institutes for Biomedical Research
Secukinumab was effective for psoriasis in two randomized phase III clinical trials, validating interleukin-17A as a therapeutic target. In the 300 mg sc dose groups, about 90% of the patients achieved a PASI 75 response at Week 16, with sustained
response rates through Week 52. Around 40% of the patients achieved complete clearance (PASI 100 response). Adverse events were comparable between dose and placebo groups.
11:20 Generation of Novel Bispecific Antibodies against TNFα and IL-17 with Different Binding Properties
Seeber, Ph.D., Principal Scientist, Large Molecule Research, Roche Pharma Research & Early Development, Roche Innovation Center Penzberg
Combined inhibition of TNFα and IL-17 show additive effects in RA-models: suppression of mesenchymal cell activation in vitro and inflammation and tissue destruction in arthritis in vivo. We further showed that combined blockade of TNFα
and IL-17 is more effective in in vitro and in vivo arthritis models. Bi-specific crossMab antibodies with 1+1 and 2+2 valences were generated and compared in vitro towards their potency for the treatment of arthritis.
11:50 ORgt Regulation of Inflammatory Cytokines in Autoimmunity
Daniel Cua, Ph.D., Senior Principal Scientist, Autoimmunity and Inflammation Merck Research Labs
The orphan nuclear receptor transcription factor RORgt is essential for TGF-b- and IL-6-dependent lineage commitment of Th17 cells. Using RORgt, IL-23R, and IL-17-eGFP reporter mice, we tracked the fate of multiple innate cell subsets critical
for maintenance of mucosal integrity and immune surveillance. We will discuss how innate lymphoid cells influence and shape the adaptive T cell responses. The significance of these findings will be discussed in the context of targeting
the IL-17 pathway for treatment of auto-inflammatory diseases.
12:20 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
Jonathan Back, Ph.D., Head, In Vivo Pharmacology, Biologics, Glenmark Pharmaceuticals
2:05 Predictive Biomarker Discovery in Proof-of-Concept Clinical Studies in Inflammatory Diseases: 3 Case Studies
Joseph R. Arron,
M.D., Ph.D., Associate Director & Senior Scientist, Biomarker Discovery, Genentech
Asthma, inflammatory bowel disease, and age-related macular degeneration are heterogeneous, which is a challenge for developing new molecularly targeted therapies. We have discovered mechanism-related predictive biomarkers identifying subsets
of patients with increased benefit in phase II proof-of-concept studies for targeted experimental therapies in each indication. Peripheral blood proteins, tissue biopsy gene expression, and genetic polymorphisms can each be used as predictive
diagnostics for inflammatory diseases.
2:35 Endpoints and Clinical Trial Design for Biologics in Autoimmune Diseases
Matthew Linnik, Ph.D., Senior Research Fellow, Autoimmunity, Eli Lilly and Company
Clinical strategies are readily available for autoimmune diseases with multiple approved treatment options. In contrast, endpoints and trial designs are less well-defined in autoimmune diseases with few approved treatment options and uncertain
regulatory requirements. This talk will critically evaluate the evolution of trial designs and endpoints in diseases like SLE, where past experience is teaching us the critical design elements and feasibility assessments needed for future
3:05 Clinical Biomarker Profile of AVX-470, an Orally Administered Gut-Targeted Anti-TNF Antibody, in Ulcerative Colitis Patients
Deborah S. Hartman,
Ph.D., Vice President, Research, Avaxia Biologics, Inc.
AVX-470 is a bovine-derived, polyclonal anti-TNF antibody with local activity in the gastrointestinal tract. Effects of AVX-470 on tissue and serum biomarkers of inflammatory activity were profiled in patients with active ulcerative colitis
in a first-in-human, double-blind, placebo-controlled clinical trial. The findings provide evidence for AVX-470 mediated reduction of inflammatory disease activity by local TNF neutralization, and support further evaluation of AVX-470
in induction and maintenance of remission of IBD.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 COVA322, a Bispecific TNF/IL-17A Inhibitor: A Next-Generation Treatment for Patients with Inflammatory Diseases
Locher, Ph.D., Chief Development Officer, Covagen AG
TNF inhibitors are well established as treatment opportunities for patients with RA, PsA and other inflammatory diseases. Anti-IL17 antibodies are in development or in the approval process and have shown considerable efficacy in almost the
same indications. There is strong evidence from animal models as well as from clinical observations that the dual inhibition of TNF and IL17 leads to a strong synergistic therapeutic effect. COVA322 is an antibody-Fynomer-fusion (FynomAb)
currently in clinical development. First safety, tolerability and efficacy data will be presented.
4:55 ARGX-113, A Novel Fc-Based Therapeutic Approach for Antibody-Induced Pathologies
Peter Ulrichts, Ph.D.,
Senior Scientist, arGEN-X BV
ARGX-113 is a proprietary antibody fragment based on arGEN-X’ ABDEG™ technology. ARGX-113 works by preventing pathogenic autoantibodies from being recycled, promoting their degradation and thereby clearing them from circulation.
Preclinical data in cynomolgus monkeys proved ARGX-113 to be highly effective in rapidly eliminating pathogenic antibodies, while sparing the broader immune response. The data support further clinical development of this novel therapeutic
approach in autoimmune disease management.
5:25 End of Conference
5:30 Registration for Dinner Short Courses