Cambridge Healthtech Institute’s Third Annual
Cancer Biotherapeutics

Immune Targeting, ADCs, Novel Engineering, and Combination Approaches

5-6 November 2015

Research for this year’s Cancer Biotherapeutics track revealed rapid developments and huge enthusiasm for immunotherapy approaches for cancer. This conference presents the FDA-approved BiTe antibody and additional developments with engaging T cells and NK cells. There is huge excitement around the mechanism of action and therapeutic potential of check point inhibitors which are providing exciting results in the clinic. Equally fascinating is CAR (Chimeric-Antigen Receptor) T cell therapy in which the patients’ cells are engineered to treat their own cancers which is also be covered in this conference. Developments with enhancing potency, stability, and half-life and with manufacturing are presented, as well as synergistic effects with ADCs.

Advances with ADCs include a platform for low-expression targets, developability assessment and the pharmacological benefits of site-specific conjugation, and also ADC/bispecific combination approaches.

This track complements the previous tracks in the Antibody Engineering Stream which include many presentations on cancer biotherapeutics, in particular bispecifics.

Final Agenda

Day 1 | Day 2 | Speaker Biographies | Download Brochure

: Unpublished Data | : Case Study

Thursday, 5 November

12:30 Registration

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

ADOPTIVE T CELL THERAPY

13:30 Chairperson’s Opening Remarks

Rakesh Dixit, Ph.D., Vice President, Safety Assessment, MedImmune (A member of AstraZeneca)

14:20 Bispecific Antibodies for Redirecting T-Cell Killing: Ag and Ab Factors Affecting the Killing Potency

Diego Ellerman, Ph.D., Senior Research Associate, Protein Chemistry, Genentech, Inc.

T cell redirected cell killing is an expanding therapeutic approach in oncology. Bispecific antibodies targeting both the T cell receptor and a tumour-specific antigen are being developed for this approach. This presentation will explore the influence of antigen density, antibody affinity and epitope distance to the membrane on the antibody potency using Her 2 and other antigen models.

14:50 Cancer Biotherapeutics - Affimers: A Novel Scaffold for Biotherapeutics

Amrik Basran, Ph.D., CSO, Therapeutics, Avacta Lifesciences

Affimers are a new protein scaffold with great potential for the generation of biotherapeutics. Based on the protease inhibitor Stefin A, large diverse libraries have been created by engineering in peptide loops into the scaffold backbone. Using phage display, we have identified competitive binders to a ranage of targets, including the immune check point, PD-L1. We have shown that the scaffold is amenable to being engineered with a range of half-life extension technologies, giving “IgG like” PK.

15:20 Refreshment Break in the Exhibit Hall with Poster Viewing

16:05 A Novel T Cell-Engaging Bispecific Format with Full-Length Antibody Properties - Applications in Cancer Immunotherapy

Seung Y. Chu, Ph.D., Associate Director, Cell Biology, Xencor, Inc.

Bispecific antibody-mediated coengagement of T cells with tumour antigens is now a proven therapeutic strategy, but inferior stability, production and half-life have hindered clinical development. We have engineered modular Fc-containing bispecifics linking a portable CD3 with full-length antibodies against many tumour antigens. I will present development case studies of several bispecifics, showing superior pharmacology and half-life in monkeys plus efficient manufacturing.

16:35 Immtacs: Bi-Specific TCR-Based Reagents for Targeted Cancer Immunotherapy

Joseph Dukes, Ph.D., Head, Preclinical Biology, Cell Biology, Immunocore Ltd.

ImmTACs are a novel class of soluble bi-specific reagents that exploit the natural antigen recognition pathway mediated by the T cell receptor (TCR), fused to a powerful effector function (anti-CD3) to redirect T-cell activity against tumour cells. This presentation will introduce the ImmTAC platform and the latest clinical data from our lead candidate, IMCgp100, currently in a Phase I/IIa trial for the treatment of malignant melanoma.

17:05 End of Day

Day 1 | Day 2 | Speaker Biographies | Download Brochure

Friday, 6 November

IMMUNE CHECKPOINTS

07:30 Morning Coffee

08:00 Chairperson’s Remarks

Stephen Beers, Ph.D., Associate Professor, Cancer Sciences Unit, Faculty of Medicine, University of Southampton

08:05 Combinations of Check-Point Inhibitors with the First-in-Class Therapeutic NK-Cell Binding TandAb AFM13 (CD30/CD16A)

Martin Treder, Ph.D., CSO, Affimed

The tetravalent bispecific TandAb AFM13 recruits and activates NK cells by specific binding to CD16A and mediates potent lysis of CD30+ tumour cells. Given promising clinical safety and efficacy data and the mechanistic involvement of immune effector cells, potential synergy with various check point inhibitors was investigated pre-clinically and will be presented.

08:35 Innovations in Cancer Biotherapeutics: Immune Checkpoint Antagonists, Agonists and Combinations

Rakesh Dixit, Ph.D., Vice President, Safety Assessment, MedImmune (A member of AstraZeneca)

The approval of one CTLA-4 and two PD-1 immune checkpoint antagonistic cancer biotherapeutics has rejuvenated the innovations in discovering and developing new immunotherapies that could increase responses and delay cancer associated deaths. The presentation will discuss the innovations in new immune checkpoint antagonists and agonists that show great promise in revolutionising cancer treatments.

09:05 T-DM1 Reinstates Anti-Tumour Immunity in HER2-Positive Breast Cancer: Synergies with α-CTLA-4 and α-PD-1

Philipp Müller, Ph.D., Project Leader, Biomedicine, University Hospital of Basel

ADCs such as the HER2-directed antibody-maytansinoid conjugate T-DM1 have emerged as one of the most powerful therapeutic formats for cancer therapy. In this presentation I will demonstrate that T-DM1 is particularly effective in eliciting anti-tumour immune responses in breast cancer patients and a HER2-expressing, syngeneic and orthotopic tumour model. Our data reveal a novel immunological mechanism of action for T-DM1 and provide a strong rationale for clinical combinations with immunotherapies.

10:35 Coffee Break with Poster Viewing

IMMUNOMODULATORY MECHANISMS / CHIMERIC ANTIGEN RECEPTOR THERAPY

11:00 Understanding How Isotype Determines the Mechanism of Action of Immunomodulatory Antibodies in the Treatment of Cancer

Stephen Beers, Ph.D., Associate Professor, Cancer Sciences Unit, Faculty of Medicine, University of Southampton

Clinical results with checkpoint-blocking mAb have revived the belief that the immune system holds the key to controlling cancer. Here we show that immunostimulatory mAb can employ multiple mechanisms in tumours, and that the mechanism used depends on mAb isotype and FcγR availability. These data have broad implications for developing immunomodulatory mAb; illustrating the necessity to determine all potential mechanisms of action to maximise activity.

11:30 A Novel IgG-Based T Cell Bispecifics Platform

Christian Klein, Ph.D., Head, Oncology Programs, Roche Pharmaceutical Research & Early Development, Roche Innovation Center Zurich

The presentation will introduce a novel IgG-based T cell bispecific (TCB) antibody platform enabled by the CrossMAb technology. Engineering, design and advantages as compared to existing T cell bispecifics platforms will be discussed. As a case study the preclinical properties of the CEA-CD3 TCB (RG7802) that is currently in Phase 1 clinical trials will be discussed.

ADC / IMMUNE CHECKPOINT COMBINATION

12:00 Chimeric Antigen Receptor Re-Directed T Cell Therapy: Biomarkers Lead the Way

J. Joseph (Jos) Melenhorst, Ph.D., Director, Product Development & Correlative Sciences, Center for Cellular Immunotherapies, University of Pennsylvania

T cells equipped with chimeric receptors (CAR) targeting tumours have evolved rapidly from a basic scientific tool to a new way in which we induce remission in patients with very poor risk cancer. The synergy between basic and translational science continues to further boost the utility of immunotherapy and enhance its potency in various forms of cancer. In my talk I will highlight recent developments in the field and conclude with how correlative studies may contribute to the success of this therapy.

12:30 Novel Cell-Based Bioassays for Analysis of mAb Fc Effector and Immune Checkpoint Functions

Vanessa Ott, Ph.D., Senior Global Product Manager, Promega Corporation

Biologics development requires unique functional and analytical tools. We have developed reporter bioassays (e.g., ADCC, ADCP, PD-1/PD-L1) that overcome limitations of primary cell assays. The bioassays offer high specificity and sensitivity, broad linearity, and robust performance, and have been implemented in high-throughput settings for mAb development, potency and stability studies.

12:45 Enjoy Lunch on Your Own

ADCs / ADC-BISPECIFIC COMBINATION

14:00 Chairperson’s Remarks

Philipp Müller, Ph.D., Project Leader, Biomedicine, University Hospital of Basel

14:05 A Plug-and-Play Approach to Antibody-Based Therapeutics via a Chemoselective Dual Click Strategy

Vijay Chudasama, Ph.D., Lecturer, Chemistry, University College London

There is clear demand for the construction of novel antibody-drug conjugate (ADC) platforms that offer greater stability, homogeneity and flexibility. A significant step towards the ideal platform for next generation antibody-based therapeutics is presented. Our technology provides decorated antibody constructs that are highly stable, with complete retention of antibody binding/structure post-modification. It combines site-specific functionalisation with exceptional versatility via a facile native disulfide targeted plug-and-play strategy.

14:35 Targeting of Solid Tumours with Bi-Specifics and Bi-Specific ADCs to Induce Novel Biologics and Drug-Like Properties

David Poon, Ph.D., Senior Director, External Research & Development and Alliances, Zymeworks, Inc.

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

15:05 Improving Potency and Stability of Antibody-Drug Conjugates

Pavel Strop, Ph.D., Associate Research Fellow, Protein Engineering, Rinat-Pfizer

Traditionally, most ADCs relied on chemical conjugation methods that yield heterogeneous mixtures of a variable number of drugs attached at different positions with an average of four drugs per antibody. The benefits of transglutaminase-based site-specific drug conjugation in terms of stability, manufacturing, improved therapeutic index and ability to generate high loaded ADCs will be discussed.

15:35 Advances and Applications of the Fleximer Platform Approach to ADCs

Tim Lowinger, Ph.D., CEO, Mersana Therapeutics

One of the challenges in developing ADCs is achieving efficacy for low-expression targets. One approach to overcome this limitation has been developed at Mersana, utilising our unique Fleximer platforms. Examples and applications will be presented to highlight the benefits of this approach to achieve greater efficacy and therapeutic index for low expression.

16:05 Developability Assessment of ADCs – A Case Study

Lars Linden, Ph.D., Head, Protein Biochemistry, Global Biologics, Cell and Protein Sciences, Bayer Healthcare

Developability analysis of antibodies and ADCs determines, together with cell line productivity and cost-of-goods analysis, the manufacturing feasibility of a drug candidate. A thorough biochemical & biophysical characterisation is performed to analyse the intrinsic stability and technical robustness of clinical candidates. Standardisation is ensured by a check of platform compatibility (DSP and analytics).

16:35 End of Conference

Day 1 | Day 2 | Speaker Biographies | Download Brochure

: Unpublished Data | : Case Study

Conference Programs

• Display of Biologics
• Engineering Antibodies
• Machine Learning - Part 2

• Antibody-Based Therapies
• Emerging Targets & Approaches
• Membrane Protein Targets

• Safety & Efficacy of Bispecifics
• Advancing Bispecifics
• Engineering Bispecifics

• Tumour Microenvironment
• Innovations in CAR Therapy
• Next-Gen Immunotherapies

• Optimisation & Developability
• Analytical Characterisation
• Protein Stability & Formulation

• Cell Line Engineering
• Expression Platforms
• Protein Process Development

• Intro to Machine Learning
• Machine Learning - Part 1
• Machine Learning - Part 2

• Intro to Machine Learning
• Intro to Bispecific Antibodies
• Intro to Protein Engineering