This track on Immunomodulatory Antibodies examines the mechanisms behind checkpoint inhibition and presents advances with a range of checkpoint blockers, with agonists, with CD3 targeting bispecifics and with targeting Fc receptors.
We present novel approaches to overcome resistance and boost the immune-stimulatory response as well as means of limiting toxicity, PK issues and auto-immune side effects. Preclinical studies, translational data and plans for entering the clinic are
included together with clinical results when available.
Final Agenda
Thursday, 22 March
08:00 Registration and Morning Coffee
08:30 Chairperson’s Opening Remarks
Ann White, PhD, Senior Principal Scientist, New Medicines, UCB
08:35 Targeting the Inhibitory Fc Receptor IIB to Boost Efficacy and Overcome Resistance to Cancer Immunotherapy
Björn Frendéus, PhD, CSO, Research, BioInvent
This talk will focus on the role of FcgRIIB in regulation of anti-cancer and immune modulatory antibody therapeutic efficacy. A lead candidate FcgRIIB antibody (BI-1206), which blocks FcgRIIB internalization and acts in synergy with rituximab
to boost responses and help overcome resistance is currently in clinical phase testing. The potential of targeting FcgRIIB to improve cancer immunotherapy in its broadest sense will be discussed.
09:05 LAG-3: Identification & Validation of the Next Generation Checkpoint Pathway
Frederic Triebel, MD, PhD, CSO & CMO, Immutep S.A.
LAG-3 is a well-known target with many checkpoint-blocking antibodies competing in the clinic. What is less known is the use of the soluble LAG-3 receptor (LAG-3Ig or eftilagimod alpha) as a MHC class II agonist to activate antigen presenting
cells (APC) and then effector CD8 T cells. Results from clinical studies with LAG-3Ig combined with paclitaxel in metastatic breast cancer (chemo-immunotherapy) or with pembrolizumab in metastatic melanoma (“pushing the gas, releasing
the brake”) will be presented.
09:35 KEYNOTE: PD-1 Antibody Is a Broad Spectrum Anticancer Therapy Both as Monotherapy and in Combination
Roy D. Baynes, MD, PhD, Senior Vice President & Head, Global Clinical Development, CMO, Merck, Sharpe & Dohme (MSD)
PD-1 antibody has shown broad activity across a number of tumor types as a monotherapy. Precision medicine enriches for those most likely to respond to monotherapy and identify those for whom alternatives such as combination therapies
should be explored. Combinations with PD-1 antibodies being explored include standard therapies (chemotherapy, radiation therapy), targeted therapies, other immunologic modulators, tumor vaccines and oncolytic viruses. The goal of
combination therapy is enhanced efficacy without compounded toxicity.
10:05 AXL Inhibition as a Potential Cornerstone of Combination Cancer Therapy
Richard Godfrey, CEO, BerGenBio ASA
AXL is a recognised target driving drug resistance and immune evasion through tumour intrinsic and immune suppressive mechanisms. Bemcentinib is a first-in-class, highly selective, oral AXL inhibitor in PhII clinical development as combination
therapy to enhance the efficacy of immune checkpoint blockade, targeted- and chemotherapy. Three trials combining bemcentinib with pembrolizumab in NSCLC, TNBC and melanoma are ongoing and a summary of preclinical and clinical data
supporting the potential for this combination will be discussed.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:35 Bispecific T-Cell Engagers (BiTE®): Update on Current Developments and Future Directions
Virginie Naegele, PhD, Senior Scientist, BiTE Technology, Amgen Research (Munich) GmbH
Among T-cell-redirecting anti-cancer approaches, blinatumomab has been clinically validated with multiple other BiTE® antibody constructs under development in various malignancies. This presentation will provide an in-depth overview
of current BiTE® development activities at Amgen.
12:05 Development of a Versatile Nanobody Based T-Cell Recruitment Platform
Stephanie Staelens, PhD, Senior Scientist, Technology, Ablynx
Small nanobodies with their modular design make a perfect starting point for generating multispecific T-cell recruitment formats. Their flexibility allows the generation of T-cell recruitment compounds simultaneously targeting
different epitopes on one tumor anchor (biparatopics) or simultaneously targeting multiple tumor antigens (bispecifics). The benign safety profile of our TCR α/β reactive recruiter was evaluated extensively both
in vitro and in vivo in non-human primates opening the opportunity for multi-specific nanobody-based T-cell recruitment therapies.
12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
12:50 Session Break
14:00 Chairperson’s Remarks
Björn Frendéus, PhD, CSO, Research, BioInvent
14:05 Costimulatory T-Cell Engagement by the 4-1BB/HER2 Bispecific PRS-343 for Tumor Localized
Activation of the Immune System
Shane Olwill, PhD, Vice President, Development; Head, Immuno-Oncology, Pieris Pharmaceutical GmbH
4-1BB (CD137) is a key costimulatory immunoreceptor and a highly promising therapeutic target in cancer. To overcome toxicity and efficacy limitations of current 4-1BB-targeting antibodies, we have developed PRS-343, a 4-1BB/HER2
bispecific based on Anticalin® technology. Here we will describe the generation and characterization of PRS-343 with regard to preclinical proof-of-concept and the preclinical dataset supporting a first-in-patient trial.
14:35 Developing Immunostimulatory Antibodies: Multiple Routes to Agonistic Function
Ann White, PhD, Senior Principal Scientist, New Medicines, UCB
Multiple monoclonal antibodies designed to stimulate tumour immunity by agonising TNFR targets are in clinical development as cancer therapeutics. In contrast to checkpoint blocking antibodies, however, agonistic agents
require more sophisticated engineering to promote their function. In this presentation, I will discuss multiple mechanisms through which mAb can stimulate signalling through TNFR, the importance of epitope specificity
and the local microenvironment, and engineering strategies that can be used to develop agents with enhanced agonistic function.
15:05 Networking Refreshment Break
15:35 Delivering Immunomodulation through OX40
Mark Cragg, PhD, Professor, Experimental Cancer Biology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton
OX40 is a costimulatory member of the TNF receptor superfamily which is seen as an attractive target for immunomodulation and cancer immunotherapy. In this talk I will discuss the use of unique human OX40 knock-in
mice, Fc receptor knock-out mice and isotype switched mAb to detail the potential utility of using anti-OX40 mAb to manipulate T-cell biology to deliver immune stimulation and immunotherapy.
16:05 OX40: The Agonist and the Ecstasy
Lucas Bailey, PhD, Principal Scientist, Protein Engineering, Invenra
The promise of combination immunotherapy has been tempered by a number of clinical setbacks and is awaiting novel approaches. We describe our B-Body™ multi-specific antibody platform screening strategy
for the discovery of an array of agonistic molecules to OX40, a receptor notorious for requiring alternative cross-linking strategies to achieve activity. Here, we demonstrate soluble bispecific antibodies
can serve as potent agonists in NFkB activation and primary T-cell assays.
16:35 Problem Solving Roundtable Breakout Discussions
Table 1: Approaches for Patients Unresponsive to Known Immunotherapy Treatments
Moderator: Mark Cragg, Ph.D., Professor, Experimental Cancer Research, Antibody & Vaccine Group, Cancer Sciences, University of Southampton
Table 2: Measures to Enhance Efficacy of Agonistic Immuno-Stimulatory Antibodies
Moderator: Ann White, PhD, Senior Principal Scientist, New Medicines, UCB
Table 3: Importance of Fc Receptor Functions and Isotype Selection for the Development of Therapeutic Antibodies for Cancer
Moderator: Gregory Driessens, PhD, Project Leader & Head, in vivo Pharmacology, iTeos Therapeutics
Table 4: Approaches to Combination Therapy
Moderator: Roy D. Baynes, MD, PhD, Senior Vice President & Head, Global Clinical Development, CMO, Merck, Sharpe & Dohme (MSD)
17:35 End of Day
18:00 Dinner Short Course Registration*
18:30 - 21:30 SC3: Preclinical Models for Cancer Immunotherapy
SC4: The Tumour Microenvironment and Response to Cancer Immunotherapy
*Separate registration required.
Friday, 23 March
08:00 Morning Coffee
08:30 Chairperson’s Remarks
Frederic Triebel, MD, PhD, CSO & CMO, Immutep S.A.
08:35 Next Generation Approaches for Stimulatory Agonists
Using Modified Antibodies
Anne Månsson Kvarnhammar, Ph.D. Senior Scientist, Alligator Bioscience
09:05 mRNA-Encoded Bispecific Antibodies for
the Treatment of Solid Tumours
Hayat Bähr-Mahmud, PhD, Scientist, Bispecific Antibodies, BioNTech AG
The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed
pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding
purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.
09:35 Anti-Tumor Efficacy and Enhancement of T-Cell Effector
Functions by EOS884448, an Antagonist Anti-TIGIT Antibody
Gregory Driessens, PhD, Project Leader & Head, in vivo Pharmacology, iTeos Therapeutics
The presentation will focus on the preclinical development of EOS884448, a new antagonist antibody targeting TIGIT receptor. Results of in vitro and in vivo assays will focus on the mechanism of action of a-TIGIT antibody and the importance of isotope selection. Finally, translational medicine data will be shared to support the selection of indication
that should benefit anti-TIGIT therapy for human application.
10:05 Biepitopic Muiltimeric Approach for Agonistic Anti-Human OX40 Antibody
Shravan Madireddi, PhD, Senior Scientific Researcher, Cancer Immunology, Genentech, Inc.
10:35 Networking Coffee Break
11:05 Avelumab (hIgG1 anti-human PD-L1)
Mediates Anti-Tumor Efficacy via Multiple Pathways in Preclinical Models
Yan Qu, PhD, Senior Principal Scientist, Rinat Pfizer
11:35 Abdurins: A New Platform for Developing Immune-Modulatory
Agents Having a Small Size and Long Half-Life to Improve Drug Concentration in Target Tissues
Kurt R. Gehlsen, PhD, Vice President and CSO, Therapeutics, Research Corporation Technologies, Inc.
We have engineered a novel antibody-like scaffold platform (Abdurins) that is small in size (12-15kDa) and retains a long serum half-life through FcRn binding. Abdurin libraries can be used to generate
highly specific binders to I/O targets, made into monospecific or multifunctional constructs and used to significantly increase drug concentration into tumors or other targeted tissues which
should lead to increased efficacy and better safety compared to full-length antibodies.
12:05 Bispecific Antibodies for Selective Blockade of
CD47 on Mesothelin-Positive Tumors
Krzysztof Masternak, PhD, Head, Biology, Research, Novimmune SA
We have developed bispecific antibodies (biAbs) pairing high affinity anti-mesothelin arms to a low affinity anti-CD47 arm. Such design restrains CD47 neutralization to mesothelin-positive cells,
limiting toxicity and pharmacokinetic issues related to ubiquitous CD47 expression. Compared to anti-mesothelin mAbs, mesothelin/CD47 biAbs induce superior ADCC and phagocytosis in vitro,
and enhanced anti-tumor responses in vivo. Mesothelin/CD47 biAbs represent a means to deliver potent efficacy safely, laying the clinical foundation for future combinat
ion therapies.
12:35 Close of Conference