Cambridge Healthtech Institute’s Second Annual

Combination Immunotherapy

Strategies and New Approaches for Better Results in the Clinic

20-21 March 2018 | Hilton London Canary Wharf | London

 

For successful Combination Immunotherapy, a better understanding is required of what is going on in the tumour, how the tumour antigens change, factors limiting the activity of T cells, and what the tumour is doing to provide an inhibitory environment.  The industry and academia are reaping the benefits of this knowledge and developing new combination approaches with new modes of action. In this track, attendees will discover how investigators are improving on the limitations of monotherapies with the application of clever combination strategies.

Final Agenda

Tuesday, 20 March

13:30 Registration

14:00 Chairperson’s Opening Remarks

David Szymkowski, PhD, Senior Research Director, Biotherapeutics, Xencor, Inc.

 

 

 

14:05 KEYNOTE: Anti-Tumor Antibody Effector Contributions to Synergistic Innate and Adaptive Immunity

K. Dane Wittrup, PhD, Carbon P. Dubbs Professor, Chemical Engineering and Biological Engineering, Massachusetts Institute of Technology

There is a mounting body of evidence that therapeutic monoclonal antibodies (mAbs) against tumor-associated antigens (TAAs) are capable of profoundly synergizing with T cell-directed immunotherapies such as checkpoint blockade and adoptive cell therapy. Two key components account for this synergy: (i) a self-vaccinal effect mediated by dendritic cells (DCs); and (ii) an inflammatory repolarization of the tumor microenvironment. Efficient exploitation of these mechanisms has tremendous therapeutic potential.

14:35 Maximising the Therapeutic Potential of Immuno-Oncology through Novel Combinations

Robert W. Wilkinson, PhD, Director, Oncology Research, MedImmune Ltd.

Significant advances have taken place in our understanding of the interplay between cancer and the immune system, and intervention points for Immuno-Oncology (IO) therapies. The talk will review the current status of IO combinatorial approaches and future areas of therapeutic advancement.

15:05 Sponsored Presentation (Opportunity Available)

15:35 Refreshment break in the Exhibit Hall with Poster Viewing

CHECKPOINT INHIBITORS IN COMBINATION

16:15 Bispecific Antibodies for Dual Immune Checkpoint Inhibition

David Szymkowski, PhD, Senior Research Director, Biotherapeutics, Xencor, Inc.

Combinations of checkpoint-blocking antibodies are more efficacious than single inhibitors, but also cause greater immune-related toxicities. We reasoned that a bispecific antibody against two checkpoints would selectively target tumor-infiltrating lymphocytes, improving safety and efficacy. We generated several dual-checkpoint inhibitors including XmAb20717 (anti-PD1 x anti-CTLA4) that are more efficacious in vivo relative to combinations of monospecific checkpoint blockers, suggesting that such bispecifics may have clinical advantages over combination therapy for the treatment of cancer.

16:45 Optimizing Dual Checkpoint Blockade through Bispecific Molecules: From Concept to Clinic

Paul Moore, PhD, Vice President, Cell Biology and Immunology, Macrogenics, Inc.

 

 

17:15 Dual Targeting of PD-L1 and TA-MUC1 in Combination with Fc-Glycoengineering as a Novel Approach to Overcome Current Limitations of Anti-PD-L1 Therapy

Johanna Rühmann, PhD, Senior Director, Internal Project Strategy & Cooperations, Glycotope GmbH

PM-PDL-GEX is a trifunctional antibody with binding sites for TA-MUC1 and PD-L1 and a functional Fc-part. By its rational construct design, the advantages of two highly effective targeting strategies are combined with respect to amplification of anti-tumor modes of action and accumulation within the tumor. The results from our in vitro proof-of-concept study further underline the potential of Fc glycol-optimization to enhance not only cytotoxic but also immunomodulatory antibody effector functions.

17:45 End of Day

18:00 Dinner Short Course Registration*

18:30 - 21:30 SC1: T-Cell Therapies: Current Field, Challenges and Future Directions

SC2: T-Cell Immunotherapy Manufacturing Development Challenges: Key Factors Shaping the Field

*Separate registration required.

Wednesday, 21 March

08:00 Registration and Morning Coffee

Treg TARGETING IN THE TUMOUR MICROENVIRONMENT TO ENHANCE IMMUNOTHERAPY

08:30 Chairperson’s Remarks

Robert W. Wilkinson, PhD, Director, Oncology Research, MedImmune Ltd.

08:35 Targeting Immune Regulation at the Tumour Site

Sergio A. Quezada, PhD, Professorial Research Fellow, Research Department of Haematology, UCL Cancer Institute

In recent years, a number of publications have demonstrated the essential role that the tumour microenvironment and Fc receptors play for the in vivo activity of checkpoint targeting antibodies. In this talk we will discuss novel development in this area relating the mechanism of action and the development of immune modulatory antibodies and combinations that promote intra-tumoural Treg with maximal modulatory activity.

09:05 Selective Targeting of Tregs in the Tumor Microenvironment

Denise L. Faustman, MD, PhD, Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School

Tregs are highly enriched in the tumor microenvironment and they are considered among the greatest barriers to successful immunotherapy because of their ability to powerfully inhibit the body’s antitumor immune response when recruited or induced by growing tumors. Non-selective approaches to targeting Tregs have resulted in autoimmune side effects common to checkpoint inhibitors. New research suggests methods for selectively targeting the Tregs unique to the tumor response as monotherapy and in combination with checkpoint inhibitors.

09:35 Problem Solving Roundtable Breakout Discussions

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

ANTI-CD27: COMBINING TUMOUR TARGETING WITH IMMUNOMODULATORY ANTIBODIES / OVERCOMING THE CHALLENGE OF TUMOUR HETEROGENEITY

11:15 Mitigating the Challenge of Tumour Heterogeneity for Meaningful Biomarker Interpretation

Abdel Halim, PharmD, PhD, DABCC, FACB, Vice President, Translational Medicine, Biomarkers and Diagnostics, R&D, Celldex Therapeutics

I will describe the probable inter- and intra-tumour heterogeneity, and explain how this makes it difficult to interpret proof-of-concept and proof-of-mechanism data, and examine possible mitigation to get useful reliable readings. Anti-CD27 agonists anti PD-1 combination therapy will be used as an example.

11:45 Enhancing Antibody Tumour Targeting with CD27 Agonists

Sean Lim, MB, ChB, PhD, Associate Professor and Honorary Consultant, Haematological Oncology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton

Monoclonal antibodies can kill tumours by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T-cell responses. Here, we explore the therapeutic potential of combining direct tumour-targeting antibodies with immunomodulating antibodies, with particular emphasis on the use of agonistic antibodies against the TNFR superfamily member, CD27. A detailed mechanistic analysis on how anti- CD27 enhances direct tumour-targeting antibodies will be presented.

12:15 Sponsored Presentation (Opportunity Available)

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:15 Session Break

13:30 Dessert Break in the Exhibit Hall with Poster Viewing

ADVANTAGES OF BISPECIFICS FOR TARGETING CHECKPOINT INHIBITORS

14:00 Chairperson’s Remarks

Sean Lim, MB, ChB, PhD, Associate Professor and Honorary Consultant, Haematological Oncology, Antibody & Vaccine Group, Cancer Sciences Unit, University of Southampton

 

 

 

14:05 Novel Combination Approaches for Cancer Immunotherapy

Christian Klein, PhD, Distinguished Scientist, Head, Oncology Programs, Cancer Immunotherapy Discovery, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich

This presentation will cover the experience with T cell bispecific antibodies, checkpoint inhibitors and immunomodulators as well as novel approaches to enhance their activity by combination therapy

14:35 Rational Combination Strategies to Augment Activity of CD3 Bispecific Antibodies

Teemu Junttila, PhD, Senior Scientist, Translational Oncology, Genentech, Inc.

CD3 bispecific antibodies induce rapid activation of T cells leading to degranulation of cytolytic vesicles and apoptosis of target expressing cancer cells. Both CD8 and CD4 cells can kill tumor cells in vitro although with distinct kinetics. T cell activation results also in feedback inhibition. PD1 up regulation has been described with multiple molecules and shown to inhibit activity of CD3 bispecific antibodies. The role of other co-inhibitory molecules is less clear. Our goal is to systematically characterize the induction and functional role of key co-inhibitory and co-stimulatory molecules upon treatment with CD3 bispecific antibodies to identify optimal combination strategies.

15:05 Targeting Immune Checkpoints with Bispecific Antibodies

John Haurum, PhD, CEO, F-star Biotechnology Ltd.

Combining immunotherapies for cancer treatment has shown numerous benefits over single agent. An attractive alternative is the development of bispecific antibodies that not only address two pharmacological targets but may also result in novel biological mechanisms that are impossible to attain with combinations. This presentation will discuss the in vitro and in vivo efficacy of bispecifics targeting immune checkpoints commonly used by cancer to evade the immune system.

15:35 Sponsored Presentation (Opportunity Available)

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing

UNIQUE COMBINATIONS

16:35 Promoting Host Anti-Tumor Immune Responses with Targeted Protein Therapeutics

Gregory P. Adams, PhD, CSO, Eleven Biotherapeutics

Targeted Protein Therapeutics (TPTs) are fusion proteins comprised of tumor-targeting antibody fragments and cytotoxic protein payloads. The ability of TPTs to directly kill tumor cells via a mechanism known as immunogenic cell death which stimulates host anti-tumor immune responses, thereby setting the stage for combination therapy with immune-oncology agents will be discussed.

17:05 Hafnium Oxide Nanoparticles and Radiotherapy to Convert Immunologically “Cold” Tumor into “Hot” Tumor

Sébastien Paris, PhD, Head, Biology, Non-Clinical, Discovery, Nanobiotix

Hafnium oxide nanoparticles (HfO2-NP) were designed to efficiently absorb ionizing radiation from within the tumor cells and augment dose deposition into the tumor. Preclinical studies have shown superior potential of HfO2-NPs exposed to radiotherapy to trigger immunogenic cell death when compared to radiotherapy. In vivo cancer models in immunocompetent mice have shown that radiotherapy-activated HfO2-NPs trigger immunogenic conversion of the tumor microenvironment while this effect is not observed with radiotherapy alone.

17:35 Towards Targeting the Tie2–αvβ3 Integrin Axis as a Novel Therapy for Angiogenesis

Niv Papo, PhD, Group Leader, Biotechnology Engineering, Ben Gurion University of the Negev

Emerging evidence has implicated increased activity of the receptor tyrosine kinase, Tie2, in the promotion of pathological angiogenesis. This activity is mediated mainly through the downstream angiopoietin (Ang)-1 and Ang2-dependent Tie2 activation of integrins, rendering the Ang/Tie2/integrins axis an attractive putative target for cancer therapeutics. To engineer inhibitors that target this axis, we developed novel single domain, non-immunoglobilin high affinity bispecific protein inhibitors against both Tie2 and αvβ3 integrin.

18:05 Close of Combination Immunotherapy