Cambridge Healthtech Institute’s 4th Annual
Combination Immunotherapy
Distinguishing Promising Cancer Immunotherapy Combinations from the Crowd
20-21 March 2019
Treating cancer patients with an immunological combination is an essential strategy that is still growing in popularity. With so many trials ongoing though, it can all get a bit confusing. There are many factors that may influence therapeutic success,
including but not limited to double immunotherapy combinations or immune checkpoint inhibitors combined with conventional cancer therapy. Predictive biomarkers, novel antigens, therapeutic mechanism, reducing toxicity and the immune response are all
important considerations. This and more will be discussed in at the Combination Immunotherapy conference.
Final Agenda
WEDNESDAY 20 MARCH
7:45 Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Daniel S. Chen, MD, PhD, Chief Medical Officer, IGM Biosciences
8:35 FEATURED PRESENTATION: Engineering Therapeutics and the Future of Cancer Immunotherapy
Daniel S. Chen, MD, PhD, Chief Medical Officer, IGM Biosciences
Single agent and combination cancer immunotherapy with PD-L1/PD-1 inhibitors have generated durable responses in a subset of patients and a survival benefit in a broad group of patients suffering from terminal cancers. However, the next generation of
cancer immunotherapeutics have not yet led to a similar therapeutic impact, potentially supporting the complexity and highly regulated nature of the human immune system. However, advances in engineered therapeutics, from cellular therapy to highly
modified multispecifc molecules, are enabling novel methods to modulating biology and the immune system to eradicate cancer.
9:05 KEYNOTE PRESENTATION: PD-1 Antibodies Are Transforming Cancer Therapy Both as Mono- and Combination Therapies
Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Sharpe & Dohme
PD-1 antibodies have shown significant activity across more than 25 major cancer types. PD-1 antibody activity in monotherapy may be enriched with precision medicine tools. Precision medicine may help define resistance biology and enable rational combinations.
Certain combinations (e.g. chemotherapy + PD-1 antibodies) may be broadly active without regard for biomarker-based selection.
9:35 CD3ε Humanized Mice: A New Tool to Validate your Bi-Specific
T Cell Engagers
Agnès Menut, Pharm D, Business Development, Protisvalor (MI-mAbs)
Manuel Pelé, PhD, Immuno-Pharmacology, MI-mAbs
Among the CD3 co-receptors chains, CD3ε is the main target of bi-specific T-cell engager. We present a first validation at MI-mAbs of a CD3ε humanized Knock-in mice model obtained by replacing mouse CD3ε
by human CD3ε, allowing in vitro and in vivo evaluation of bi-specifics targeting human.
9:50 Immunotoxicity Assessment in a Circulating Human Whole
Blood System
Erika Fletcher, PhD, Head of Research and Development, Immuneed
Immuneed offers a whole blood loop model where all the blood components are present, including intact cascade systems. Pre-clinical characterization of biotherapeutics in a physiologically-relevant model that mimics circulation is key for better understanding
of the function and safety of candidate drugs and to increase the likelihood of clinical success.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 NEW: IgA-Mediated Tumor Killing Can Be Further Enhanced by Blocking the Innate Immune Checkpoint SIRPa
Mitchell Evers, MSc., PhD student, Immunotherapy group, laboratory for translational immunology, University Medical Center Utrecht
All clinically used mAb are of the IgG class but IgA can be very effective in vitro and in vivo, with a distinct mechanism of action: IgA has the unique capacity to activate neutrophils, our most abundant but often underappreciated white blood cell.
For a long time, it was hard to produce and purify enough IgA for preclinical experiments. Furthermore, IgA has a short half-life and mice lack the IgA receptor which hampers the preclinical research. In the presentation these issues will be addressed
and answered, with preclinical examples for lymphoma and neuroblastoma. Furthermore, the combination with innate checkpoint inhibitors will be discussed
11:15 Bispecific Antibodies for Tumor-Directed Blockade of CD47, a Ubiquitously Expressed Immune Checkpoint
Stefano Majocchi, PhD, Research Scientist & Project Leader, Research Department, Novimmune SA
To evade the immune system, cancer cells overexpress CD47, a ubiquitous innate immune checkpoint. Bispecific antibodies afford selective tumor-directed CD47 targeting, allowing for an improvement of therapeutic window as compared to monospecific strategies,
such as anti-CD47 mAbs and SIRP alpha-Fc fusion proteins. In vivo translational studies demonstrate that tumor-directed blockade of CD47 with bispecific antibodies results in enhanced anti-tumor activity and a modification of the properties of
the tumor microenvironment.
11:45 The Use of Bispecific Antibodies to Modulate Anti-Tumour Immune Responses
Melanie Medcalf, PhD, Senior Scientist, Drug Discovery, F-star Biotechnology Ltd
mAb² ™ is a bispecific antibody format that allows a “plug and play” modular strategy F-star product strategy to address heterogeneity of tumour phenotypes in vitro and in vivo efficacy of F-star bispecific antibodies targeting oncology pathways.
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:45 Dessert Break in the Exhibit Hall with Poster Viewing
13:15 Session Break
14:00 Chairperson’s Remarks
Johan Lantto, PhD, Project Director, Immuno-Oncology, Symphogen
14:05 On the Requirement to Induce Immune Modulation Prior to Checkpoint Inhibitor Therapy: Lessons from Mice and Men
Angus Dalgleish, MD, FRCP, FRACP, FRCPath, FMedSci, Foundation Professor of Oncology SGUL, Principal of the Institute of Cancer Vaccines and Immunotherapy,
Institute of Infection and Immunity, St George’s University of London
Checkpoint inhibitors (CPIs) have revolutionized the treatment of several cancer types, however, the majority of patients do not benefit on single agent CPIs. Mouse studies show that response to CPIs do not occur unless innate immune cells are activated
and other markers are reduced. IMM-101 activates innate immune responses and has been reported to enhance clinical responses to CPIs in melanoma patients.
14:35 Regulatory Challenges and Opportunities for Combination Development
Elena Spanjaard, PhD, Global Head of Regulatory Affairs, Regulatory Affairs, Celyad
Efficient co-development of novel combination therapies presents complex regulatory challenges. Regulatory guidelines provide a framework for development of investigational agents that are intended for use in combination. Key considerations for selecting
combination agents and modality-specific considerations will be highlighted. Current special regulatory designations and expedited pathways will be reviewed, including qualifying criteria, features, and benefits.
15:05 Problem Solving Roundtable Discussions
Why Are IO-Combination Therapies Harder to Develop than Anticipated?
Moderator: Alexander Eggermont, MD, PhD, Professor Surgical Oncology, University Paris-Sud; Director General, Direction, Gustave Roussy Comprehensive Cancer Center
Optimal Checkpoint Combinations
Moderator: Angus Dalgleish, MD, FRCP, FRACP, FRCPath, FMedSci, Foundation Professor of Oncology SGUL, Principal of the Institute of Cancer Vaccines and Immunotherapy, Institute of Infection and Immunity, St George’s University of London
16:05 Refreshment Break in the Exhibit Hall with Poster Viewing
16:35 Lessons from Melanoma and the Development of Combination Immunotherapies
Alexander Eggermont, MD, PhD, Professor Surgical Oncology, University Paris-Sud; Director General, Direction, Gustave Roussy Comprehensive Cancer
Center
The immune checkpoint inhibitors (ICIs) anti-CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) and anti-PD1/anti-PDL1 (programmed death-1 receptor and its ligand PD-L1) are the basis of an unprecedented development of successful immunotherapies across
many tumor types. Melanoma has been at the frontier of this development where within 7 years, advanced melanoma was transformed into a curable disease in over 50% of patients.
17:05 Discovery and Development of Antibody Combinations for Cancer Immunotherapy
Johan Lantto, PhD, Project Director, Immuno-Oncology, Symphogen
Immune checkpoint blockade using monoclonal antibodies targeting CTLA-4 and the PD-1/PD-L1 axis has shown impressive efficacy in the treatment of various cancers. However, since only a subset of the patients responds to these therapies, search
for other relevant targets, and development of more powerful therapeutic combinations has become an intense area of focus. Here, we present Symphogen’s approach to discovery and development of potent antibody combinations for cancer
immunotherapy.
17:35 Safety Issues in Combinatorial Immunotherapy Trial Design
Ioannis Karydis, BM, BCh, MA, DPhil, MRCP, Associate Professor in Medical Oncology, Cancer Sciences, University of Southampton
The last decade has seen a rapid paradigm shift in clinical trial design; a number of innovative approaches have accelerated the process of bringing a novel agent from lab to clinic. Development of immunooncology agents has benefited from these,
however the unique characteristics of these agents pose specific challenges when it comes to determining their safety profile. This talk will summarise the issues at play and present ways to address them.
18:05 Networking Reception in the Exhibit Hall with Poster Viewing
19:05 Close of Day
THURSDAY 21 MARCH
8:00 Morning Coffee
8:30 Chairperson’s Opening Remarks
Graham Pockley, PhD, CEO, multimmune GmbH; Professor of Immunobiology, John van Geest Cancer Research Centre, Nottingham Trent University
8:35 NK Cell-Based Therapy for the Treatment of Tumours Expressing Membrane Hsp70
Graham Pockley, PhD, CEO, multimmune GmbH; Professor of Immunobiology, John van Geest Cancer Research Centre, Nottingham Trent University
Despite progress, significant numbers of individuals continue to die of aggressive, therapy-resistant disease. Professor Pockley will introduce a new natural killer (NK) cell-based approach for the treatment of aggressive cancers which express
a membrane form of Hsp70 – ‘one drug could indeed fit all’.
9:05 Targeting Deubiquitylating Enzymes (DUBs) at the Immuno-Oncology Interface
Benedikt Kessler, PhD, Professor of Biochemistry and Life Science Mass Spectrometry, Nuffield Department of Medicine, University of
Oxford
Enzymes that bind and process ubiquitin, a small 76 amino acid protein, have been recognized as pharmacological targets in oncology and immunological disorders. Mass spectrometry technology has now reached the capacity to cover complete proteomes,
and modification by ubiquitin can be profiled in sufficient depth to interrogate deubiquitylating (DUB) and conjugating E3 enzyme substrates. We have studied ubiquitin specific protease 7 (USP7) and its role in the p53 tumour suppression axis
and controlling FOXP3 levels in regulatory T-lymphocytes. We show that small molecule inhibition of USP7 affects cancer cell growth as well as the balance between regulatory and effector T-cells, indicating a new class of reagents for immunotherapy.
9:35 Immune Checkpoints Humanized Preclinical Models for Biologics’ Efficacy and MoA
Kader
Thiam, Vice President of Transgenic Technologies Business, genOway
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 The Exercise of Taming the Immune System
Per Thor Straten, PhD, Professor, Department of Hematology, Center for Cancer Immune Therapy, University Hospital Herlev
We have characterized a novel co-stimulatory pathway in CD8 T cells. The stimulatory signal goes via activation induced surface expression of both the receptor as well as the soluble ligand. Importantly, increased signaling via this pathway leads
to increased cytokine release and proliferation, whereas blocking of the pathways by monoclonal antibody or siRNA technology leads to diminished production of TNF-α and INF-γ, as well as and reduced proliferation.
11:15 Novel Patterns of Response to Combination Immunotherapy in Cancer Patients
Christophe Le Tourneau, MD, PhD, Head, Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France
Patterns of response to immunotherapy differ from conventional treatments. These patterns include durable responses, even after treatment interruption, rare pseudoprogressions, hyperprogressions that need an early assessment of patients, and dissociated
responses for which local treatments might be discussed. Immune-related response criteria only address the question of progression. We will discuss how combination immunotherapy might impact these patterns of response.
11:45 NEW: Rational Immuno-Oncology (IO) Combination Therapy
Matthew Robinson, PhD, Associate Director, R&D Oncology Unit, AstraZeneca
Immuno-Oncology (IO) therapy, such as immune checkpoint blockade antibodies, has created a paradigm shift in the treatment of some cancers. Our understanding around biomarkers of which patients will benefit from IO therapy continues to evolve;
alongside how best to modulate the anti-cancer immune response through rational/data driven combinations with other IO therapies (targeting innate and/or adaptive immune cells), targeted therapies and/or standard of care treatments, such
as chemo- and radio-therapy.
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:45 Dessert Break in the Exhibit Hall with Poster Viewing
13:30 Close of Combination Immunotherapy