Significant scientific advances in the fields of immunology and protein science are driving the development of biotherapeutic drugs in a growing range of therapeutic areas beyond oncology. These advances are driving the identification of new and unique
targets, new approaches to developing biotherapeutics for unserved medical needs, methods of binding to illusive targets and translational science for patient stratification and drug development for niche indications. The PEGS Emerging Indications for Therapeutic Antibodies conference
provides a forum for research organizations with diverse portfolios to explore new science and technology in the development of a next generation of safe and effective therapeutics in an important set of emerging indications.
MONDAY, APRIL 8
7:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Opening Remarks
Catherine Hutchings, PhD, Independent Consultant, United Kingdom
8:40 Synthetic Antibody Fragments as Sensors and Modulators of GPCR Activation and Signaling
Arun Shukla, PhD, Chair, Professor and EMBO Young Investigator Intermediate Fellow, Wellcome Trust DBT India Alliance, Indian Institute of Technology, India
G protein-coupled receptors (GPCRs) constitute the largest class of cell surface receptors and they are targeted by majority of currently prescribed medicines. We have developed and characterized a series of synthetic antibody fragments through Phage
Display technology platform that can report GPCR activation with spatio-temporal resolution and modulate selective functions in cellular context.
9:10 Production of Inhibitory Antibody Against Claudin-5 using Engineered Membrane Protein Antigens
Hiroyuki Takeda,
Ph.D., Associate Professor and Principal Investigator, Division of Protea-Drug-Discovery Sciences, Proteo-Science Center, Ehime University, Japan
The production of antibodies against extracellular regions (ECR) of membrane proteins is notably difficult because of the low productivity and immunogenicity of membrane proteins. We overcome these problems by using protein engineering and cell-free protein
production technology. Immunization of engineered claudin-5 (CLDN-5) ECR antigens induced CLDN-5 ECR-binding antibodies with a high rate. Five monoclonal antibodies against CLDN-5 ECR were produced from immunized mice, and one clone successfully inhibited
CLDN-5-dependent tight junctions.
9:40 Pipeline Update on GPCR and Ion Channel Antibodies
Catherine Hutchings,
PhD, Independent Consultant, United Kingdom
G protein-coupled receptors (GPCRs) and ion channels represent some of the most important target classes for therapeutic drug discovery across a wide range of diseases. The progress made by antibody-based therapeutics directed to these target classes
will be reviewed outlining the breadth and diversity of antibody molecules, target opportunities in R&D and the clinical pipeline, including recent development to the expansion of opportunities afforded by next-generation modalities.
10:10 Networking Coffee Break (Harbor & Mezzanine Level)
10:50 Amplifying Antibody Function with Nanomaterials for Inflammation and Autoimmune Therapy
Tarek Fahmy, PhD, Associate
Professor of Biomedical Engineering and Immunobiology, Yale University
Antibody therapy (armed or unarmed) as a “magic bullet” dates back to Paul Ehlirch in the late 1800’s. To date, the “magic bullet” continues to be challenging to implement in a general manner for treatment of inflammation
and autoimmune disease remission. I’ll discuss a paradigm-shift in amplifying antibody function using small packages called, “nanoparticles” loaded with drugs or biologics and targeted to regulatory immunity. The methodology overcomes
several limitations with conventional antibody therapy.
11:20 Novel Anti-CD20 Antibodies for Treating Autoimmune Disease and Hematologic Malignancies
Alexey Misorin,
Senior Research Associate, Antibody Discovery, BIOCAD, Russian Federation
We have developed monoclonal antibodies against CD20 for treating autoimmune diseases – BCD-132, and for treating hematologic malignancies – BCD-171. BCD-132 and BCD-171 interact with extracellular part of CD20 antigen with nanomolar affinity
and demonstrate desirable properties in vitro. We will present results from a phase I study of BCD132 in which we evaluated pharmacokinetics, pharmacodynamics, safety and immunogenicity of our antibodies.
11:50 KEYNOTE PRESENTATION: Lessons Learned from Humira
Jochen Salfeld,
PhD, Vice President, Global Biologics; Distinguished Research Fellow, AbbVie
The presentation will focus on the evolution of therapeutic Anti-TNF approaches, the history of adalimumab and will start to answer the question how to explain some of the apparent clinical differences between the Anti-TNF agents in clinical use today.
In this context the learnings about TNF biology and the mechanism of action of TNF antagonists will be discussed and how those learnings impact the development of novel therapeutics.
12:20 pm A Multiplatform Strategy for the Discovery of Modulating Antibodies Against Ion Channel Targets
Yelena Bisharyan, Director, External Alliances, Tetragenetics, Inc.
Identifying antibodies that block ion channels is a challenging endeavor exacerbated by difficulties in producing recombinant ion channels in amounts that support drug discovery programs. We have developed a strategy to address this challenge by combining
high-level expression of these proteins with immunization of diverse species and unique screening tools.
12:35 Longitudinal, Event-Based, Same-Day Sample Collection: The Implications for Biomarker Development
Brian Neman, CEO, Sanguine Biosciences
Sanguine partners with patients and leverages their health data to accelerate your research for their condition. By working together with patients, directly, Sanguine is able to perform home visits, and to easily retrieve medical records, on their
behalf. 500+ completed studies. 20/40 top pharma. 30,000+ patients.
12:50 Luncheon Presentation I: Developability: Evaluating Specificity, Immunogenicity, Functionality & Manufacturability For Lead Candidate Selection
Campbell Bunce, Senior Vice President, Scientific Operations, Abzena
Understand the latest series of in silico computational models, analytics, in vitro and ex vivo experiments used in developability assessment. Characterise a molecules Specificity, Immunogenicity, Safety, Functionality and Manufacturability. Data
generated informs sequence, structural, formulation and process refinements to select the best candidate for manufacture.
1:20 Luncheon Presentation II: Development of Active and Passive Immunization Strategies for Preventing HIV Infection
Mauricio Martins, PhD, Assistant Professor, Biology, University of Miami
Despite improvements in prevention strategies and antiretroviral therapy coverage, thousands of new HIV infections are still occurring every day, underscoring the need for effective anti-HIV immune interventions. Here I will describe how my laboratory
has been developing and testing immunization strategies against HIV in rhesus macaques (RMs). In the first part of the talk, I will show how we used a new vaccine modality to elicit protective immunity against a highly pathogenic simian immunodeficiency
virus (SIV) molecular clone. This vaccine regimen consisted of DNA plasmids delivered by intramuscular electroporation and replication-competent forms of rhesus monkey rhadinovirus (RRV)–a herpesvirus that establishes persistent infection
in RMs. In the second part of the talk, I will go over our plans to gene therapy to prevent mother-to-child transmission (MTCT) of HIV. Specifically, we will use adeno-associated virus (AAV) vectors to transfer genes encoding HIV-specific broadly-reactive
neutralizing monoclonal antibodies (bnMAbs) newborn RMs. AAV vectors have emerged as safe and versatile gene therapy tools that can transduce both dividing and non-dividing cells. Given the long lifespan of muscle cells (average: 15 years), skeletal
muscle is a preferred tissue for AAV-mediated gene transfer. Thus, a single intramuscular injection of AAV/bnMAb vectors at birth might result in long-term production of bnMAbs for years, possibly decades. Achieving this outcome in infants would
dramatically simplify efforts to prevent MTCT of HIV. We hope that the HIV immunization approaches described here will provide new insights into how to generate persistent immunity against HIV.
1:50 Session Break
2:20 Problem-Solving Breakout Discussions - Click here for details(Commonwealth
Hall)
3:20 Networking Refreshment Break (Harbor & Mezzanine Level)
4:00 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, MedImmune
PLENARY KEYNOTE SPEAKER
4:10 Vision for How Immunotherapy Will Shape Future of Cancer Care
Leena Gandhi, MD, PhD, Vice President, Immuno-Oncology Medical Development, Lilly Oncology
Immunotherapy is considered by many as a pillar of cancer care today, but in many ways we have only scratched the surface. Our knowledge and understanding of the complexities of immunotherapy and its mechanisms continue to evolve. The future of cancer
care will be defined by our ability to systematically identify and implement opportunities for combination therapy to improve and standardize patient response.
YOUNG SCIENTIST KEYNOTE
4:55 The Lassa Virus Glycoprotein: Stopping a Moving Target
Kathryn Hastie, PhD, Staff Scientist, Immunology and Microbiology, The Scripps Research Institute
Lassa virus causes ~5000 deaths from viral hemorrhagic fever every year in West Africa. The trimeric surface glycoprotein, termed GPC, is critical for infection, is the target for neutralizing antibodies, and a major component of vaccines. Structural
analysis of Lassa GPC bound to antibodies from human survivors reveals a major Achilles heel for the virus and provides the needed template for development of immunotherapeutics and improved vaccines.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:15 End of Day
TUESDAY, APRIL 9
8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:25 Chairperson’s Remarks
Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, Biochemical Pharmacology, Queen Mary University, United Kingdom
8:30 Direct Targeting Cytosolic Proteins by IgG-Format Antibody
Yong Sung
Kim, PhD, Professor, Molecular Science & Technology, Ajou University, Korea
Our group recently developed a platform technology of a cytosol-penetrating antibody (cytotransmab), which in the IgG format can reach the cytosolic space of living cells owing to its endosomal escaping ability after receptor-mediated endocytosis.
Based on the cytotransmab technology, we have engineered a human IgG1 format antibody, named iMab, which specifically internalizes into the cytosol of tumor cells and then selectively binds to targeted cytosolic proteins, including oncogenic
Ras mutants.
9:00 Targeting Microvesicles Loaded with Drugs to Arthritic Joints Using Antibodies Specific to Arthritic Cartilage
Ahuva Nissim,
PhD, Professor, Antibody and Therapeutic Engineering, Biochemical Pharmacology, Queen Mary University, United Kingdom
Microvesicles (MV) are extracellular vesicles released from the plasma membrane of cells. We loaded MV with antibody specific to damaged arthritic cartilage (anti-ROS-CII). After assessing incorporation and in vitro functional validation, in vivo localization and treatment experiments using mouse model of arthritis were successfully performed. MV targeted by anti-ROS-CII loaded with combined treatment significantly accelerated
resolution of inflammation. Thus, targeted MV may be developed as a ‘magic bullet’ to safely treat diseases.
9:30 V565, an Oral Anti-TNFα Domain Antibody for IBD
Tim Carlton, PhD, Associate Director, Research, VHsquared, United Kingdom
V565 is an anti-TNFα domain antibody for oral administration in IBD patients, derived from a llama single domain antibody and engineered for intestinal protease resistance. Ex vivo biopsy studies, measuring
changes in phosphoprotein levels, and oral dosing studies in man demonstrate that V565 is highly potent, stable throughout the intestine and able to penetrate the disrupted colonic mucosa and neutralize membrane and soluble TNFα at the
site of active disease.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:50 Antibody Responses to Influenza in Context
Patrick
C. Wilson, PhD, Professor, Medicine & Rheumatology, Knapp Center for Lupus and Immunology Research, Committee on Immunology, University of Chicago
Influenza infections are a leading cause of death and illness. Current vaccines to influenza are insufficient because of changes in viral antigenicity. Recent work will be discussed on the characterization of human B cell and antibody responses
to influenza. This work has led to key insights that should allow improvements to influenza vaccines and to identify monoclonal antibodies that could be used therapeutically.
11:20 Antibody-Antibiotic Conjugate against Staphylococcus Aureus: Mechanism and Modulation of Activity
Wouter Hazenbos, PhD, Scientist, Infectious Diseases, Genentech
Complicated Staphylococcus aureus infections can be difficult to treat, as bacteria may reside in intracellular reservoirs, limiting antibiotic access. We generated an antibody-antibiotic conjugate, comprising an antibody binding
S. aureus, conjugated to a rifamycin-analog through a cathepsin-cleavable linker. This molecule kills S. aureus inside host cells, and is superior to standard antibiotics in mouse infection. Current work focuses on MOA; new
technology to enhance activity; applicability to other pathogens.
11:50 Structure-Based Approaches for the Discovery of Potent Antibodies against Malaria Antigens
Jean- Philippe Julien, PhD, Canada Research Chair in Structural Immunology, The Hospital for Sick Children Research Institute
Reverse vaccinology holds promise to design effective immunogens for the development of malaria vaccines. This concept is based on interrogating B cell repertoires to identify inhibiting antibodies that will guide immunogen design. Our research
focuses on characterizing protective antibodies of high potency against malaria antigens at the bottlenecks of transmission between the mosquito vector and human host. These studies also have implications for the development of antibody interventions
against malaria.
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 (Commonwealth Hall)
2:00 Chairperson’s Remarks
Anthony Shock, PhD, Director, Immunology Research, UCB, United Kingdom
2:05 Anti-Cytokine Therapy for Atherosclerosis
Paul M. Ridker,
MD, MPH, Eugene Braunwald Professor of Medicine, Harvard Medical School; Director, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital
Recently, the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) has demonstrated that specific targeting of interleukin-1beta can significantly lower cardiovascular event rates with no effect on cholesterol or blood pressure. Moreover,
the magnitude of clinical benefit was related to the robustness of inflammation inhibition. Thus, we now have proof of principle for the inflammation hypothesis of atherothrombisis and a signal for multiple new treatment targets.
2:35 Targeting FcRn in IgG Autoantibody-Driven Diseases
Anthony
Shock, PhD, Director, Immunology Research, UCB, United Kingdom
The neonatal Fc receptor, FcRn is responsible for rescuing IgG from lysosomal degradation and is responsible for the long half-life of this protein in vivo, but FcRn is also responsible for recycling pathogenic
IgG autoantibodies. Rozanolixizumab is a high affinity IgG4P mAb targeting FcRn, developed to specifically inhibit the recycling of IgG and is demonstrating clinical efficacy in patients with IgG autoantibody-driven diseases.
3:05 MutaMap®, a Mutational Activity Map for Optimum Protein Design
Emilee Knowlton, PhD, Immunology, Sales Specialist, Sales, ProImmune Inc.
MutaMap® is an in vitro assay system that helps explore the effect of substituting each amino acid in at each position in a protein sequence one by one with all 19 possible substitutions and find out the effect
on protein activity. MutaMap® allows you to make informed protein engineering decisions for a range of key developability objectives, including; Improving activity/affinity, de-immunization, altering cross reactivity, improving humanization
and prolonging half-life of your protein.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:25 Completing the Immunity Cycle by Developing Myeloid Immunotherapies
Tatiana Novobrantseva, PhD, Co-Founder, Head of Research and Development, Verseau Therapeutics
Macrophages/DCs are biologically optimized to either induce or suppress an immune response. Targeting pro-tumorigenic macrophages has been repeatedly identified as a very important next step of development for the field of immuno-oncology. Similarly,
myeloid cell suppression has been long realized to be fueling the vicious cycle of the autoimmune disease. The talk will describe Verseau Therapeutics’ approaches to tweaking myeloid cell functionality in human disease.
4:55 Antagonistic Antibodies Used to Establish the Key Role for IL-13 Signaling Via the Type 2 IL-4 Receptor in Experimental Atopic Dermatitis
Itai Benhar, PhD,
Professor, Molecular Cell Biology and Biotechnology. Tel-Aviv University
IL-13 and IL-4 are potent mediators of type 2-associated inflammation such as asthma and atopic dermatitis (AD) and share a receptor subunit, IL-13Ra1 which is part of IL-4R. The role of the type 2 IL-4R in AD remains to be defined. We show that
oxazolone-induced AD in mice is dependent on the type 2 IL-4R and targeting of the type 2 IL-4R using an IL-13Ra1-neutralizing antibody alleviates oxazolone-induced AD.
5:25 End of Emerging Indications for Therapeutic Antibodies
5:30 Registration for Dinner Short Courses (Commonwealth Hall)
Recommended Dinner Short Course*
SC11: Developability of Bispecific Antibodies: Formats and Applications
Nimish Gera, PhD, Director, Research and Development, Mythic Therapeutics
*Separate registration required.