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Track 2 Novel Approaches for Cancer

Track 2


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Tuesday, 15 March


RETARGETING T CELLS WITH BISPECIFICS

13:00 Conference Registration

14:00 Chairperson’s Opening Remarks

Stefan Dübel, Ph.D., Managing Director and Professor, Biotechnology, Technische Universität Braunschweig

14:05 Preclinical Evaluation of a CD3/CD33-Bispecific T-Cell-Engaging Antibody with Potential for Treatment of Acute Myelogenous Leukemia

Matthias FriedrichMatthias Friedrich, Ph.D., Director, Nonclinical Development, Amgen Research (Munich) GmbH

CD33 has been frequently selected as target antigen for acute myeloid leukemia therapy. AMG 330 is a Bispecific T-cell engager (BiTE®) antibody construct mediating redirected lysis of CD33-postive cells by cytotoxic T cells. In vitro and in vivo studies support clinical development of AMG 330 for the treatment of acute myeloid leukemia.

14:35 Bispecific TCR-Anti-CD3 Fusions for Potent Re-Directed Killing of Cancer Cells: Safety and Efficacy Evaluation Using Assessment in a Predictive in vitro Preclinical Package

Luise_WeigandLuise Weigand, Ph.D., Team Leader, Cell Biology/Research Management, Immunocore Ltd.

ImmTACs are bispecific pico-molar affinity T-cell receptors fused to an anti-CD3 specific scFv that re-direct a potent T-cell response towards its target. Here we present how we approach our in vitro preclinical package, used to evaluate safety and efficacy, and the predictability of this process for our most advanced molecule IMCgp100 currently in a Phase I/II study.

15:05 A κλbody Bispecific Platform Approach that Tethers Blockade of the ‘Don’t Eat Me’ Signal to Cancer Cells

Marie Kosco-VilboisMarie Kosco-Vilbois, Ph.D., CSO, Novimmune SA

To overcome potential pharmacological and clinical liabilities of universally targeting CD47, we have developed bispecific κλ bodies, which selectively target CD47 on cancer cells. These κλ bodies are full-length bispecific IgGs that bind with high affinity and neutralise CD47 on cancer cells expressing a tumor-associated antigen (TAA), thus, focusing cell killing to cancer cells. Currently, various κλ bodies are in development, e.g., for B cell malignancies (CD47/CD19) and mesothelin-positive tumors (CD47/Mesothelin).

15:35 Q&A with Session Speakers

15:50 Refreshment Break with Exhibit and Poster Viewing


IMMUNOMODULATORY BISPECIFICS

16:30 Discovery and Characterisation of Immunomodulatory Bispecific Antibodies

Mark ThrosbyMark Throsby, Ph.D., CSO, Merus BV

The Biclonics® platform is a robust and validated technology suite for the development of human full length IgG bispecific antibodies. In this presentation we will outline how the technology has been applied to generate bispecific antibody candidates against checkpoint inhibitory and costimulatory molecules.


17:00 Development of a Bispecific Targeting EGFR and CTLA-4

Neil Brewis, Ph.D., CSO, F-star Biotechnology Ltd.

F-star creates unique Fcab™ antibodies by engineering the constant region against a single target, which can be combined with the variable regions of differing antibodies to create a bispecific. This technology was used to generate a constant region against EGFR and combining with the variable domain of CTLA-4. The ensuing EGFR/CTLA-4 bispecific showed efficacy in an in vivo model compared to either EGFR or CTLA-4 alone.

17:30 CEA TCB, a Novel T-Cell Bispecific Antibody for the Treatment of Solid Tumors

Marina BacacMarina Bacac, Ph.D., Head, Cancer Immunotherapy, Roche Innovation Center Zurich.

CEA TCB is a new generation T-cell bispecific antibody for the treatment of CEA-expressing solid tumors. Its activity correlates with CEA expression level resulting in efficient elimination of high CEA-expressing tumour cells and sparing of primary epithelia. CEA TCB is efficacious in vivo in poorly-T-cell infiltrated solid tumors. It converts non-inflamed into highly-inflamed tumors accompanied by T-cell re-localisation from the periphery into tumor bed. The combination with PD-L1 enhances CEA TCB activity.

18:00 End of Day One of Novel Approaches for Cancer

18:00 Dinner Short Course Registration

18:30 – 21:30 Dinner Short Courses*


SC1: Cancer Immunotherapy

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

Andrea van Elsas, Ph.D., CSO, BioNovion B.V.

SC2: Engineering and Optimisation of Antibody Products

Nicolas Fischer, Ph.D., Head, Research, Novimmune SA

Stefan Dübel, Ph.D., Managing Director and Professor, Biotechnology, Technische Universität Braunschweig

 *Separate Registration Required.


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Wednesday, 16 March


DEVELOPMENTS WITH FUSION PROTEINS

08:30 Chairperson’s Remarks


KEYNOTE PRESENTATION

8:35 Antibody-Cytokine Fusion Proteins (Immunocytokines)for Targeted Delivery: From Bench to Phase III

Dario NeriDario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Zurich

Antibody-cytokine fusion proteins (“immunocytokines”) are a promising class of immunomodulatory agents, which are currently being considered for the treatment of cancer and of chronic inflammation. In this lecture, I will present aspects of our preclinical and clinical experience with immunocytokines specific to splice isoforms of fibronectin and of tenascin-C.

09:05 Multivalent Antibody-TRAIL Fusion Proteins for Cancer Therapy

Roland KontermannRoland Kontermann, Ph.D., Professor, Biomedical Engineering, Cell Biology and Immunology, University of Stuttgart

Fusion of TRAIL to antibody fragments has been shown to allow for a targeted delivery and the selective induction of tumour cell death. We have engineered optimised single-chain derivatives of TRAIL and different homodimerisation models to develop novel multivalent antibody-scTRAIL fusion proteins with improved properties. Targeting and controlled dimerisation of scTRAIL fusion proteins provides a strategy to enforce apoptosis induction, together with retained tumor selectivity and good in vivo tolerance.

09:35 Problem Solving Roundtable Discussions

Table 1: Antibodies that Harness the Immune System

Moderator: Kerry Chester, Ph.D., Professor, UCL Cancer Institute

  • Target selection criteria
  • Engineering challenges
  • Relevant animal models
  • How to overcome the challenges of scale, safety and efficacy

Table 2: Pros and Cons of Armed Antibody Products

Moderator: Dario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Zurich

  • Benefits of different types of product in terms of potency, stability and versatility regarding targets and use in combination therapies
  • Pros and cons of intact antibodies versus scaffolds
  • Choice of target: membrane proteins versus extracellular matrix proteins
  • Delivery considerations

Table 3: Screening of Antibody Libraries

Moderators: John McCafferty, Ph.D., CEO, IONTAS

Stefan Dübel, Ph.D., Managing Director and Professor, Biotechnology, Technische Universität Braunschweig

  • Display technologies for the creation of antibody libraries
  • Tailored selection and screening strategies
  • Antibody library designs for affinity optimisation

Table 4: Overcoming the Challenges of ADCs and Technologies for the Construction of Next Generation ADCs

James Baker, Ph.D., Senior Lecturer, Chemistry, UCL

  • How to select the right linker and toxin for your product
  • Challenges with linkers
  • Novel drugs and payloads
  • Challenges with site-specific conjugation
  • Safety concerns and challenges with toxicity
  • Optimization of stability, potency, specificity and homogeneity

10:35 Coffee Break with Exhibit and Poster Viewing


TECHNOLOGIES FOR TARGETS AND LEAD SELECTION

11:15 Chairperson’s Remarks

Kerry ChesterKerry Chester, Ph.D., Professor, UCL Cancer Institute

 

 

 

 


FEATURED PRESENTATIONS

11:20 Engineering Antibodies and T-Cell Receptors by Mammalian Display

John McCaffertyJohn McCafferty, Ph.D., CEO, IONTAS

Generation of immune-modifying binders is facilitated by the availability of large libraries of antibodies or T-cell receptors expressed on the surface of mammalian cells. We demonstrate the construction and use of mammalian display libraries, facilitated by the use of site-specific nucleases. Such libraries allow the screening of millions of clones by flow sorting while providing information on both the level of expression and the extent of binding within individual clones.

11:50 Comprehensive Human Antibody Libraries and Human Effector Fusions: Impact on Next Generation Cancer Therapeuticals

Stefan DübelStefan Dübel, Ph.D., Managing Director and Professor, Biotechnology, Technische Universität Braunschweig

Two decades of antibody engineering have brought substantial gains in knowledge on how to make good human antibodies for therapy, but also on obstacles to their clinical use. It has also become evident that IgG alone cannot cure cancer in most cases, which has sparked the search for additional and novel effector mechanisms. We present our newest advances in both human antibody generation and effectors.


MaxCyte12:20 High Expression of Bispecific Tandem scFvs and Tribody [(Her2)2X CD 16] in CHO Cells Transfected via Scalable Electroporation
Peer Heine, Ph.D., Field Application Scientist, MaxCyte. Inc.
Moving bispecific antibodies from the bench to the clinic requires a scalable process that is consistent and reproducible while delivering a biologically active bispecific antibody. Flow electroporation is a universal, high-performance transient transfection technology that is a proven means of producing high titers and high quality bispecific antibodies at both small and large scale. In this presentation, data will be presented comparing the production of bispecific antibodies by reagent-based transfection and the MaxCyte STX(r) Scalable Transfection System in CHO-S cells. In addition, data on transient expression of bispecific tandem scFv (in a bispecific T cell-engaging (BiTE)-like format) molecules in CHO cells also will be presented. Plasmids encoding bispecific tandem scFvs targeting CD19 and CD3 or Her2 and CD3 were transfected into CHO-S cells via static electroporation. Proteins purified from conditioned media via affinity chromatography exhibited specific target cell and effector cell binding, and they facilitated T-cell mediated lysis of tumor cells in functional assays. Overall, we demonstrate how flow electroporation technology can produce biologically active bispecific antibodies at small and large scale.

12:50 Luncheon Presentation (Sponsorship Opportunity Available) Or Lunch on Your Own

13:20 Session Break

14:00 Chairperson’s Remarks

Kerry Chester, Ph.D., Professor, UCL Cancer Institute


DEVELOPMENTS WITH ADCs

14:05 Chemical Platform for the Construction of Highly Defined Therapeutic Antibody Conjugates

James Baker, Ph.D., Senior Lecturer, Chemistry, UCL

A powerful and general chemical platform technology is described for the construction of highly defined antibody conjugates by site-selectively targeting and bridging the interchain disulfide bonds. This approach allows access to antibody-drug conjugates, designed to release potent cytotoxins specifically at targeted cancer cells, with a controlled drug to antibody ratio (DAR) and high serum stability. Insights will also be given into the scope for further applications e.g. in bispecifics, imaging, radioimmunoconjugates etc.

14:35 Development of Natural Product Derived Splicing Inhibitors as Antibody Drug Conjugate Payloads

Sujiet PuthenveetilSujiet Puthenveetil, Ph.D., Principal Scientist, Medicinal Chemistry, Pfizer, Inc.

Analogs of the natural product spliceostatin are highly potent spliceosome inhibitors with a novel mechanism of action that are currently being explored as payloads for antibody drug conjugates (ADCs) for the treatment of cancer. A medicinal chemistry initiative was greatly facilitated by an optimized fermentation process that produced gram quantities of these payloads allowing for subsequent linker attachment, conjugation and screening to yield highly efficacious ADCs. We will describe the early challenges with efficacy and safety of this class of molecule and how these were overcome by synthesis and conjugation efforts.

15:05 Endogenous Vaccination: Kadcyla Renders HER2+ Breast Cancer Highly Susceptible to Immune-Checkpoint Blockade

Philipp MüllerPhilipp Müller, Ph.D., Lab Head, Biomedicine University & University Hospital of Basel

ADCs such as Kadcyla harbour the potential to act as an endogenous anti-tumour vaccine. In this presentation I will demonstrate that Kadcyla is particularly effective in eliciting anti-tumour immunity in a HER2-expressing, orthotopic tumour model and breast cancer patients. Our data reveal a novel immunological mechanism of action for this class of ADC and provide a strong rationale for clinical combinations with immune-checkpoint blockade.

15:35 Refreshment Break with Exhibit and Poster Viewing


ROLE OF DENDRITIC CELLS IN IMMUNOTHERAPY / ROBUST MODELS FOR TRANSLATIONAL STUDIES

16:00 Clinical Trials with mRNA Electroporated Dendritic Cells for Stage III/IV Melanoma Patients

Kris Thielemans, Ph.D., Professor, Immunology & Oncology, Vrije Universiteit Brussel

We present convincing data of the clinical responses induced by a “next generation” dendritic cell based immunotherapy, in combination with checkpoint blockade and in an adjuvant setting.


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16:30  Close of Conference




For more details on the conference, please contact:

Nicole Lyscom, Ph.D.
Senior Conference Director
Cambridge Healthtech Institute
Tel: +44 7791 866489
Email: nlyscom@healthtech.com

For partnering and sponsorship information, please contact:

Companies A-K
Jason Gerardi
Business Development Manager
781-972-5452 | jgerardi@healthtech.com

Companies L-Z 
Carol Dinerstein
Director, Business Development
781-972-5471 | dinerstein@healthtech.com

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20-24 March 2017


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CONFERENCE PROGRAMS


DINNER COURSES

"Some of the most promising emergent biopharmaceuticals for cancer therapy include agents capable of selective homing to the tumor environment, as well as drugs capable of selective activation of the immune system against malignant cells."

Dario Neri, Ph.D., Swiss Federal Institute of Technology


"You have put together an amazing meeting."

Sergio A. Quezada, Ph.D., UCL Cancer Institute