Cambridge Healthtech Institute’s 2nd Annual

Cancer Biotherapeutics
Immune Modulation, Bispecifics, ADCs, Synergistic Mechanisms and Unique Approaches
6-7 November 2014


Speaker BiographiesDownload Brochure | Register 

Research in 2014 for this event reveals a huge increase in interest in immunotherapy and much continued interest in bi-and multi-specific products, combination approaches, and antibody drug conjugates. This conference track will present advances in all of these areas from discovery to development, and provide details on innovative modes of action, and on application and efficacy.  Safety considerations for these new approaches will also be covered.

Thursday, 6 November

12:30 Conference Registration

13:00 Dessert Break in the Exhibit Hall with Poster Viewing


TARGETING THE IMMUNE RESPONSE

13:30 Chairperson’s Opening Remarks

Janine SchuurmanJanine Schuurman, Ph.D., Vice President, Research, Genmab


KEYNOTE PRESENTATION

13:35 Safety Challenges and Risk Mitigation Strategies to Develop Immune Activating Biologics

Rakesh DixitRakesh Dixit, Ph.D., Vice President, Research and Development, Safety Assessment, MedImmune LLC

This presentation will cover: how immunotherapy may result in autoimmune and off-target toxicities to self versus tumours; combining immunotherapy with other agents; how to maximize the efficacy and balance safety vs. efficacy; measures to streamline the combined approach and reducing toxicity to self; and strategies to risk mitigate safety concerns with the immune activating biologics and their combination.


14:05 ImmTACs: TCR-Based Bispecific Reagents for Targeted Cancer Therapy

AnneliseVuidepotAnnelise Vuidepot, Ph.D., Head, Protein Science, Immunocore Ltd.

ImmTACs are soluble bispecific-TCR-anti CD3 fusions suitable for the treatment of several tumour types. Unlike antibodies, TCRs target MHC-bound peptide antigens derived from endogenously processed proteins, providing a large pool of intracellular antigens from which to select appropriate target molecules. Our most advanced program is in the treatment of malignant melanoma and is currently in a phase IIa clinical trial.

Randox Pharma Services14:35 Camelid Single Domain Antibody Fragments to Cardiac Troponin I: A Case Study

Shirley Schön, Ph.D., Team Leader Recombinant Antibodies, Molecular Biology, Randox Laboratories Ltd.

Camelid single domain antibodies (sdAbs) are small and highly stable recombinant antibody fragments with activity and specificity equivalent to standard monoclonal antibodies. We present data on the isolation, properties and adaptability of alpaca sdAbs to cardiac troponin I. Randox can offer a custom sdAb isolation, humanization and engineering service.

15:05 Refreshment Break in the Exhibit Hall with Poster Viewing


TARGETING THE IMMUNE RESPONSE (continued)

15:45 Targeting Cancer with BiTE Molecules

Roman KischelRoman Kischel, M.D., BiTE Technology, Amgen Research (Munich) GmbH

The recent clinical success in harnessing the immune system to fight cancer has demonstrated the potential of this approach. Here we will give an overview of the BiTE (Bispecific T-cell Engager) technology, which drives directed T cell mediated tumour cell killing, and describe our target discovery platform.

16:15 Targeting Immune Checkpoints in Cancer: Novel Mechanistic Insights on the Role of Fc Receptors and the Tumour Microenvironment

SergioQuezadaSergio A. Quezada, Ph.D., Professorial Research Fellow, Research Haematology, University College London Cancer Institute

The immunological balance in cancer is often characterized by dominant infiltration of regulatory T cells. Antibodies against CTLA-4, a key immune modulatory receptor expressed on T cells, efficiently modify this balance promoting tumour elimination. Surprisingly, changes in Teff/Treg ratio and tumour rejection depend on the depletion of tumour-infiltrating Treg cells expressing high levels of CTLA-4. Depletion is driven by FcγRIV expression on tumour infiltrating myeloid cells illustrating the impact of Fc Receptors and the tumour microenviroment on the final outcome of antibody-based immune-modulatory therapies.

16:45 Discovery and Development of Fusion Proteins and Antibodies Modulating the Immune Response in Malignancy and Enhancing Overall Effector Function

SolLangermannSol Langerman, Ph.D., CSO, Research and Development, Amplimmune, Inc.

AMP-224 binds to inhibitory receptor PD-1. It was extensively tested in a CT26 colon carcinoma model, prior to human studies and found to be maximally active (60% tumour free survival) when administered once or twice a week, after receiving a single, low dose of cyclophosphamide (CTX). This promoted a functional anti-tumour immune response. A variety of clinical correlative studies were run to assess biological activity of the molecule, using real-time immune-monitoring assays and readouts.

17:15 End of Day One

17:15 Dinner Short Course Registration

17:30 – 20:30 Dinner Short Courses

Recommended Short Courses*

SC6: Troubleshooting and Engineering of Antibody Constructs

SC7: Immunotherapy Approaches

SC8: Recent Advances in Antibody-Drug Conjugates

*Separate Registration Required.




Friday, 7 November

08:00 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee


BISPECIFIC ANTIBODIES FOR CANCER

08:30 Chairperson’s Remarks

Rakesh DixitRakesh Dixit, Ph.D., Vice President, Research and Development, Safety Assessment, MedImmune LLC





08:35 Targeting of Solid Tumours with Bispecifics and Bispecific ADCs – Inducing Novel Biologics and Drug-Like Properties

DavidPoonDavid Poon, Ph.D., Director, External R&D and Alliances, Zymeworks, Inc.

A robust, developable and manufacturable bispecific platform will be discussed as the foundation to engineer novel anti-solid tumour antibodies. Unlike combination therapies, these bispecifics demonstrate enhanced tumour decoration, tumour diffusion and retention, internalization, and effector functions. Supported with IND-enabling in vivo efficacy studies, Zymeworks’ lead bispecific and bispecific ADC programs will be presented.

09:05 Preclinical Developments with a Fully-Human Bispecific Antibody Platform

Eric SmithEric Smith, Ph.D., Associate Director, Bispecific Antibodies, Regeneron Pharmaceuticals, Inc.

This presentation will describe a platform technology to generate fully human bispecific antibodies through the combination of Fc modifications that allow selective protein A purification and VelocImmune® derived antibodies that utilize a single defined light chain. Molecular characterisation and initial in vitro efficacy data will be discussed. In addition, preclinical findings with proof-of-principle molecules targeting T cells will be presented.


09:35 Problem Solving Roundtable Discussions

Key Features of a Bispecific Antibody Platform

DavidPoonModerator: David Poon, Ph.D., Director, External R&D and Alliances, Zymeworks, Inc.

  • Importance of a versatile platform that allows you to understand the biology. (The trick is to find the right platform that allows you to test different target combinations.)
  • Importance of manufacturing enough for bench scale while keeping an eye on feasibility for large-scale manufacturing
  • Importance of ensuring simplicity of manufacturing
  • Mouse models are well validated – show survival and efficacy. Always some risk of immuno.

Antibody-Drug Conjugates: Linkers and Payloads

GoncaloBernardesModerator: Gonçalo Bernardes, Ph.D., Royal Society, University Research Fellow, Chemistry, University of Cambridge

  • Novel payload strategies
  • Measures to enhance efficacy, safety and tolerability
  • Means of finding a good target and matching the target with the payload and linker
  • Overcoming resistance, and matching payload to target population
  • Toxicity, especially prediction of off-target toxicity
  • What are the critical issues for taking ADCs into the clinic

Safety Concerns with Immunotherapy

Rakesh DixitModerator: Rakesh Dixit, Ph.D., Vice President, Research and Development, Safety Assessment, MedImmune LLC

  • How real is the danger of autoimmunity and off-target toxicity?
  • How do you balance safety versus efficacy
  • Measures to reduce negative effects
  • Risk mitigation strategies

Strategies for Entering the Clinic

SolLangermannModerator: Sol Langerman, Ph.D., CSO, Research and Development, Amplimmune, Inc.

  • Developing the right translational strategy for prediction in humans – in vitro and ex-vivo testing
  • Setting up the clinical trial with a high degree of integrity to capture samples in a time-sensitive manner.
  • proof of concept studies; dose and efficacy data
  • Validation of the mechanism of action and efficacy.
  • Why cancer biotherapeutics so often fail in phase 3

Fc Engineering to Enhance Complement Activation

Janine SchuurmanModerator: Janine Schuurman, Ph.D., Vice President, Research, Genmab

  • What happens in complement activation and why some products are better than others for this
  • Different approaches applied (comparison of MOAs, different Fc receptors, recruitment of different cells
 

10:35 Coffee Break


DEVELOPMENTS WITH ADCs

11:00 Discovery of Novel Linkers, Payloads and Antibody-Drug Conjugates for the Treatment of Cancer

EdmundGrazianiEdmund I. Graziani, Ph.D., Associate Research Fellow, Oncology Medicinal Chemistry, Pfizer, Inc.

Antibody-drug conjugates (ADCs) are an emerging modality for the treatment of cancer. Presently, three classes of cytotoxic payloads have been successfully employed on these modalities in clinical settings, namely the auristatins, maytansines and calicheamicins. This talk will focus on Pfizer’s chemistry strategy to discover and develop new linker-payload classes and conjugation technologies that will yield more efficacious and potentially better tolerated conjugates that we are advancing to the clinic.

11:30 Producing Homogeneous ADCs with Single or Combination Warheads

AaronSato2Aaron Sato, Ph.D., Vice President, Research, Sutro Biopharma, Inc.

Using Xpress CF+, hundreds of non-natural amino acid antibody variants are made within a day. Using fast, quantitative conjugation chemistries, e.g. Click Chemistry/Reverse Diels-Alder, antibodies are conjugated within hours with low molar excess of linker warhead. The best sites are selected based on expression, cell binding, conjugation efficiency (DAR), and cell killing. In vivo efficacy, PK/PD, and stability studies further winnow to our best ADC candidates. Multiple ADC examples will be provided that illustrate the power of this platform.

12:00 Targeted Delivery of Cytotoxic Agents for Cancer Treatment

GoncaloBernardesGonçalo Bernardes, Ph.D., Royal Society, University Research Fellow, Chemistry, University of Cambridge

Our work explores the interplay between effector molecules, targeting ligands and site-selective protein conjugation chemistry to create safer, more selective and efficient cancer therapeutics. This lecture will cover recent examples of emerging areas in our group in (i) targeted drug conjugates construction with an emphasis on traceless antibody-drug conjugates and (ii) use of carbon monoxide (CO) as an immunomodulator signalling molecule for applications in cancer therapeutics.

12:30 Sponsored Presentation (Opportunity Available)

13:00 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


COMPLEMENT ACTIVATION, SYNERGISTIC MECHANISMS, ENHANCED ADCC, AND CLINICAL DEVELOPMENTS

14:00 Chairperson’s Remarks

SergioQuezadaSergio A. Quezada, Ph.D., Professorial Research Fellow, Research Haematology, University College London Cancer Institute





KEYNOTE PRESENTATION

14:05 The Mechanism of Complement Activation by IgG Antibodies

Janine SchuurmanJanine Schuurman, Ph.D., Vice President, Research, Genmab

Complement activation by antibodies is an important mechanism in immune defense and immunotherapy. Using X-ray crystallography, mutagenesis studies and cryo-EM tomography, we revealed that IgG antibodies form hexamers on the cell surface following antigen binding. Enhancing hexamerisation on the cell surface by using the HexaBody platform potentiated the intrinsic killing capability of antibodies in in vitro, in vivo and ex vivo models.


14:35 IgA as a Novel Antibody Isotype for the Treatment of Cancer, Potential Synergy with IgG Antibodies

Jeanette_LeusenJeanette Leusen, Ph.D., Associate Professor, Translational Immunology, University Medical Center, Utrecht

Our lab has recently shown that IgA can induce efficient killing of EGFR-positive tumour cells in vivo, in mice transgenic for the human receptor for IgA, FcaR. We are now studying the combination of IgG and IgA antibodies against Her2 and EGFR, and find that they work synergistically. It is hypothesized that the combination of effector cells and mechanisms is responsible for this synergy.

15:05 ARGX-111, a Defucosylated Antagonistic Anti-MET Antibody, Displays Potent Anti-Tumour Activity through Enhanced ADCC

NatalieDeJongeNatalie de Jonge, Ph.D., Senior Scientist, arGEN-X

Signaling through MET, the hepatocyte growth factor (HGF) receptor, plays a key role in tumour progression and metastasis. In cancer patients, molecules blocking HGF/MET induce incomplete blockade of MET, are primarily associated with cytostatic activity, and result in modest clinical effects. To overcome this limitation, we developed a defucosylated anti-MET antibody that blocks both HGF-dependent and independent MET activation mechanisms, and kills MET-expressing cancer cells through enhanced ADCC.

15:35 Clinical Development of Tanibirumab and its Next Generation of Bispecific Antibody

Jin-SanYooJin-San Yoo, Ph.D., CEO and President, PharmAbcine, Inc.

Tanibirumab, a novel anti-KDR neutralizing fully human IgG has completed a Phase I study. In contrast to other KDR pathway antagonists, Tanibirumab does not cause hypertension, hemorrhage and bleeding side effects, and due to its cross-species cross reactivity, it has been assessed in in vivo efficacy studies. These allow precise design of clinical trial protocols. Currently we are planning Phase II trials, and developing bispecific next-generation products to enable Tanibirumab to reach its full potential.

16:05 End of PEGS Europe



Speaker BiographiesDownload Brochure | Register