The second part of the program will address the challenging circumstance of identifying novel approaches that can be used to enter the thriving immune-oncology space. The meeting will begin with a broad look at current understandings of the biology of
immune-oncology and what has been learned from the many recent clinical studies in the space – and then explore specific opportunities related to new and underexplored targets, improvements in target selectivity and unmet medical needs. Special
consideration will also be given to the translation of academic and clinical stage findings into commercial development programs. A discussion format will offer those in attendance a novel opportunity to explore strategies in this space with colleagues.
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RECOMMENDED ALL ACCESS PACKAGE:
Choose 2 Short Courses
or 1 Symposium and 2 Conferences/Training Seminars
Thursday, September 27
11:50 am Conference Registration Open (Foyer)
12:20 pm Plenary Keynote Program
2:00 Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)
2:45 Welcome Remarks
Kent Simmons, Senior Conference Director, Cambridge Healthtech Institute
2:50 Chairperson’s Opening Remarks
Thomas Bouquin, PhD, Head, Biologics Research, Sanofi, France
2:55 KEYNOTE PRESENTATION: Diverse Biologics Modalities Underpin ‘Third Wave’ Cancer Immunology Therapeutics
Jonathon Sedgwick, PhD, Vice President and Global Head, Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharmaceuticals
Despite over a century of research, it has only been in the current decade that using the patient’s own immune system to attack and remove cancer as a reliable and effective therapeutic approach has succeeded, through use of so-called “checkpoint
inhibitor” monoclonal antibodies. Additional approaches to enable the immune system to recognize and kill cancer cells are being investigated. Diverse biologics modalities dominate the field, and these will be discussed.
3:25 Emerging Technologies for Personalizing Cancer Immunotherapy
Aaron Goldman, PhD, Instructor in Medicine, Harvard Medical
The ability to predict whether a patient will respond to treatment is a ‘holy grail’ for oncologists. The vision and strategy for the 21st century treatment of cancer calls for a personalized approach in which therapy selection is
designed for each individual patient. Here, we profile emerging models, systems and platforms that seek to harness the complexity of the tumor microenvironment to provide solutions for the clinic.
3:55 Agonist Bispecific Antibodies Delivering the Next Immuno-Oncology Breakthrough
John Haurum, PhD, CEO, F-Star, United Kingdom
Targeting T cells via TNFRSF costimulatory pathways has the potential to strongly activate the immune system due to broad expression across multiple immune cells. However, FcR-mediated crosslinking is often required for optimal activity, limiting
clinical efficiency, due to low affinity of Fc:FcR interactions and ADCC-mediated T cell depletion. We will present novel bispecific programmes that do not bind to FcR, but instead crosslink their two targets, resulting in a potent and controlled
T cell activation.
4:25 Refreshment Break in the Exhibit Hall with Poster Viewing (Grand Ballroom)
5:00 Droplet-Microfluidics as a Powerful Tool for Cancer Immunotherapy
Merten, PhD, Group Leader, Microfluidics, European Molecular Biology Laboratory (EMBL), Germany
Droplet-microfluidics allows assays to be carried out at high throughput, using minute amounts of sample material (e.g., patient biopsies). In this talk, I will show how these conceptual advantages can be exploited in cancer immunology, e.g.,
for the discovery of tumor-associated antigens (TAAs) and personalized therapy approaches.
5:30 Antibody Discovery for Novel Multi-Targeting Strategy in Immuno-Oncology
Thomas Bouquin, PhD, Head, Biologics Research, Sanofi, France
Targeting the first generation of immune checkpoints pathways has revolutionized cancer treatment leading to durable responses in previously not curable patients. However, many patients and cancer types do not respond to these treatments,
prompting the discovery of new classes of immunotherapies. The presentation will focus on our strategy to discover antibodies against next-generation targets in the immune oncology space and their combination in our proprietary multi-specific
6:00 Genome-Wide Networks of Stem Cell-Associated Retroviral Sequences Define Novel Diagnostic and Therapeutic Targets in Clinically Lethal Malignancies
Gennadi V. Glinsky, MD, PhD, Research Scientist,
Institute of Engineering in Medicine, University of California, San Diego
Stem cell-associated retroviral sequences (SCARS) define thousands of genetic regulatory elements that emerged during human genomes’ evolution from endogenous retroviruses, and genome-wide, SCARS shaped the evolution of human-specific
genomic regulatory networks (GRNs). Experimental and clinical evidence documenting the critical role of SCARS and associated GRNs in pathogenesis of clinically intractable human malignancies will be reported with an emphasis on molecular
and genetic definitions of novel diagnostic and therapeutic targets.
6:30 Dinner Short Course Registration (Foyer)
9:30 Close of Day
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Friday, September 28
7:00 am Registration Open (Foyer)
7:30 Interactive Breakfast Breakout Discussion Groups - View Details
Room: Back Bay A
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.
Table 18: Considerations in Selecting Bispecific Antibody Formats for Immunotherapies
Moderator: Gundo Diedrich, PhD, Director, Antibody Engineering, MacroGenics
- Target considerations in selection of bispecific pairs
- Criteria to select a format: valency, half-life, effector function
- Manufacturing challenges: byproducts, aggregation, titer
- Considerations to modulate the affinity to both targets: cis vs. trans-binding, target expression
- MOAs of bispecifics that cannot be addressed with combinations of monospecific antibodies
Table 19: Considerations in Target Selection for Antibody-Drug Conjugates (ADCs)
Moderator: Jennifer J. Hill, PhD, Team Lead, MS & NMR Analytics, National Research Council Canada
- Characteristics of real-world ADC targets and how these compare to the ideal ADC target
- Prediction and screening methods to determine target suitability for ADC development
- ADC target expression in healthy tissues: what is acceptable?
- Matching targets with optimal drug-linkers
Table 20: Going Beyond Dual Antibody Targets to Tackle the Complexity of Cancer and the Immune System
Moderator: Marc Mansour, PhD, Senior Consultant, Leidos Health
- Could single targets (e.g., PD-1/ PDL-1) and dual targets (e.g., PD-1 and CTLA4) be the exception rather than the rule for effective immune modulation of cancer?
- Combining antibody-based therapies with other modalities such as other biologics or small molecules/targeted therapies – can we do better than simply follow rational (but generally blind) development plan?
- How do we assess success in our search of a clinical signal when testing complex combinations?
8:30 Chairperson’s Remarks
Joseph Rucker, PhD, Vice President, Research and Development, Integral Molecular, Inc.
8:35 ErbB Targeted CAR-T Cell Immunotherapy of Head and Neck Cancer: T4 Immunotherapy
John Maher, PhD, Clinical Senior Lecturer in Immunology, Kings
College London, United Kingdom
T4 immunotherapy consists of a CD28+CD3 zeta-based chimeric antigen receptor (CAR), targeted against the extended ErbB network, and which is co-expressed with an IL-4 responsive chimeric cytokine receptor. Preclinical efficacy and safety has
been demonstrated in models of head and neck, ovarian, breast cancer and mesothelioma. Phase I clinical evaluation is now ongoing in patients with locally advanced or recurrent head and neck cancer, employing intra-tumoral delivery to
9:05 Development of DART and TRIDENT Molecules to Target Costimulatory and Checkpoint Receptors for Immuno-Oncology Applications
Gundo Diedrich, PhD, Director, Antibody Engineering,
Bispecific molecules offer unique opportunities for the treatment of cancer that cannot be replicated with monospecific antibodies. The development of bispecific DART and TRIDENT molecules for dual checkpoint inhibition (PD-1 x LAG3, PD-1
x CTLA4) and tumor localized immune cell agonism (HER2 x CD137) will be presented. A synthesis of how these novel agents can be combined with other cancer treatments in an integrated immune stimulatory approach will be discussed.
9:35 Targeting the Innate Immune System to Improve the Outcomes of PD-1/PD-L1 Therapy
Kathleen M. Mahoney, M.D., Ph.D., Clinical
Instructor, Beth Israel Deaconess Medical Center; Research Associate, Dana Farber Cancer Institute
Blocking either the PD-1 receptor or its ligand PD-L1 has improved overall survival in Phase III trials in patients across tumor types. While some tumors fail to response due to a lack of immune cells infiltrating the tumor, others fail
despite immune cells in the tumor. The microenvironment of many “hot” tumors is hostile to antitumor lymphocyte activity, in part due to the myeloid cell population, including tumor-associated macrophage and myeloid-derived
suppressor cells. By targeting these innate immune cells via pathways such as CSFR1 or VISTA, we may be able to improve the responses and durable outcomes of PD-1/PD-L1 therapy for patients with these “hot” tumors.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced (Grand Ballroom)
10:45 A Microbiome-Derived Dual Checkpoint Inhibitor with Anti PD-1 Activity Enhances T Cell Activation and Antitumor Immunity
Marc Mansour, PhD, Senior Consultant, Leidos
LD01, is a microbiome-derived small peptide with dual checkpoint activity against PD1 and one other synergistic receptor. LD01 increases T cell proliferation in the presence of PDL-1. In challenge models, systemic LD01 reduced B16-F10
lung metastases, protected animals from sepsis, and enhanced vaccine-induced malaria specific T cells leading to enhanced survival from malaria. LD01 has broad utility as a stand-alone immunotherapeutic and as a genetically engineered
component of other therapies.
11:15 T-DM1-Resistant Cells Gain High Metastatic Potential: Identifying Novel Therapeutic Targets for the Treatment of T-DM1-Resistant Disease
Wen Jin Wu, MD, PhD, Senior Investigator, Office of Biotechnology
Products, Center for Drug Evaluation and Research, FDA
T-DM1 is an ADC approved to treat trastuzumab-resistant breast cancers. Despite initial favorable outcomes, most patients eventually progress disease due to development of acquired resistance to T-DM1. We found that T-DM1-resistant
cells gain high metastatic potential with significantly increased cell motility and invasion and that integrin proteins play critical roles in the regulation of cell invasion. We proposed that targeting integrins may be a novel
therapeutic approach to treat T-DM1-resistant disease.
11:45 Completing the Immunity Cycle by Developing Myeloid Immunotherapies
Tatiana Novobrantseva, PhD, Co-Founder, Head, 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.
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 (Grand Ballroom)
1:55 Chairperson’s Remarks
Kris F. Sachsenmeier, PhD, Associate Director, Translational Science, AstraZeneca
2:00 The TGFb Pathway as a Resistance Mechanism of Immune-Checkpoint Inhibitors and Novel Targets in the TGFb Pathway
Kuldeep Neote, PhD, Senior Director, New Ventures/Scout J&J Innovation Center Boston
The hallmarks of resistance to PD-1/PD-L1 blockade is a low mutational burden, T cell exclusion or a TGFb activated stroma. TGFb has been shown as an important driver of checkpoint blockade re-sistance in metastatic melanoma and
urothelial cancers, but development of TGFb antagonist-based therapies has been hampered by systemic toxicity. The presentation discusses strategies to neutralize TGFb in the tumor microenvironment that have the potential of
limiting systemic toxicity and reverse immune evasion typified by a T cell exclusion phenotype.
2:30 Overcoming Specific Mechanisms of Resistance to Immuno-Oncology Therapies
Kris F. Sachsenmeier, PhD,
Associate Director, Translational Science, AstraZeneca
As the clinical use of immunotherapies increases, knowledge of specific mechanisms of resistance are coming into focus. A review will be presented which summarizes a number of widely-accepted immuno-oncology resistance mechanisms,
including tumor micro-environmental immunosuppression, activation or inactivation of specific signaling pathways and changes in tumor HLA status and antigen presentation. Theoretical means of addressing each resistance mechanism
will also be reviewed within the current context of preclinical and clinical experience.
3:00 Indirect Immunization with Antigen-Specific Monoclonal IgG & IgE: Schedule-Dependent Interactions with Cytotoxic Agents and Immune Modulators
Christopher F. Nicodemus, MD,
Chairman, Clinical & Scientific Advisory Board, OncoQuest, Inc., Canada - View Speaker Intervieweazwqvdacavf
We examined the properties of Fc-gamma and Fc-epsilon constructs and identified molecules to initiate CD8 T cell Immunity that translates into promising preclinical and clinical antitumor activity in a schedule-dependent fashion
linked to administration of cytotoxic and select immune adjuvants. IgE shows additional promise in mobilizing NK cell activity at low doses and influencing tissue perfusion of solid tumor tissue matrix. Lead products targeting
Muc1 and Muc16 for a range of indications are discussed.
3:30 Selection of Antibody-Drug Conjugate Targets Using Expression Data, Glycoproteomics, and Functional Screens
Jennifer J. Hill, PhD, Team Lead, MS &
NMR Analytics, National Research Council Canada
Antibody-drug conjugates (ADCs) are a promising therapeutic class for cancer therapy. We describe our approach to identify new ADC targets, incorporating gene expression data mining and glycoproteomic profiling, followed by
in vitro screening through a surrogate ADC assay. Based on these target selection methods, we are producing thousands of monoclonal and single-domain antibodies generated against a variety of cancer-associated
targets and screening them for ADC activity, in vitro and in vivo.
4:00 Close of Conference
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