Cambridge Healthtech Institute’s Third Annual

Immunomodulatory Antibodies

Harnessing the Immune Response and Overcoming Inhibitory Factors

22-23 March 2018 | Hilton London Canary Wharf | London

 

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

CHECKPOINT BLOCKADE: MEASURES TO ENHANCE EFFICACY

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 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

T-CELL REDIRECTION AND RECRUITMENT

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

AGONISTIC RECEPTOR ENGAGEMENT AND IMMUNOSTIMULATORY APPROACHES

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

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

NEXT GENERATION APPROACHES

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

Jeong Kim, PhD, Scientist & Group Leader, Genentech, Inc.

 

 

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 Sponsored Presentation (Opportunity Available)

10:35 Networking Coffee Break

ENHANCEMENT OF PRODUCT PROPERTIES

11:05 Mode of Action, Enhancement of Stability, and Determination of Specific Delivery for Immuno-Oncology Products Targeting Agonists and/or Cytokines

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 combination therapies.

12:35 Close of Conference