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September 26-28 2017
The Seaport Hotel and WTC, Boston, MA

Day One
Wednesday September 27 2017

Day Two
Thursday September 28 2017

08.00
Registration & Networking

08.20
Chair’s Opening Remarks

08.30
Lessons Learned from the Clinical Development of Bispecifics

Synopsis

  • Investigating strategies to ensure the successful development of bispecifics in the context of unpredictable biologies and outcomes
  • Understanding how clinical experience can feed back and improve earlier development
  • Case study: overcoming unexpected immunogenicity of anti-TNF therapeutics – transferrable lessons to enhance your bispecific development

09.00
Engineering Bispecific Antibodies for Cancer therapy – a Unique Perspective for Pediatric Solid Tumors Spanning Three Decades

Synopsis

  • Contrasting how conventional IgG monoclonal antibodies (mAbs) relying on Fc-dependent mechanisms are constrained by low killing potency, poor cell trafficking, and inefficient epitope spread, whereas bispecific antibodies (BsAb) have the potential to turn circulating polyclonal T cells into tumor infiltrating cytotoxic T cells despite the immunosuppressive tumor microenvironment
  • Understanding how BsAb allows T-cell mediated immunotherapy to bypass the need for the expression of HLA and of costimulatory molecules on tumor targets, as well as prior immunization
  • Exploiting BsAb to deliver massive doses of radiation in multistep targeting with vastly improved therapeutic ratios

09.30
Speed Networking & Morning Refreshments

11.00 Information Content & Molecular Complexity: Importance of Library Design to Selection Results

  • Investigating how bispecific antibodies often require specific binding modes from their individual components to maximize potency and efficacy
  • Analyzing the effect of library design and size on the outcome of a selection for component of a tri-specific anti-HIV-1 entry inhibitors
  • Sharing insights into how large and carefully designed libraries can increase the probability of success when selecting for a molecule with specific functional features

Jonathan Davis, Principal Scientist, Protein Design, Bristol-Myers Squibb

11.30 Optimization of Binding Strengths in a Tissue-Targeted Erythropoietin

  • Understanding how binding features of parent molecules may not be optimal in a bispecific.
  • Investigating how weak/moderate binding plus avidity can enhance specificity and how binding constants can affect both PK and signaling activity
  • We need a new roadmap for quantitative optimization of elements in multidomain engineered proteins.  We are working in a multidimensional landscape and need new design approaches beyond simply increasing throughput

Jeffrey Way, Senior Staff Scientist, Wyss Institute, Harvard University

11.00 A New Mechanism of Action for Bispecific Antibodies Activating Tumor-Specific Antigen T Cells

  • Novel proprietary ex vivo assay for bispecific antibodies (BsAbs) in hematological malignancies patient samples
  • BsAbs can generate CTLs that kill tumor independent of BsAb and target, probably tumorspecific antigen CTLs immunosuppressed in bone marrow, same as TILs in solid tumors
  • New design of multi-specific antibodies from new MOA empowered by the screening of 100s of constructs ex vivo
  • Novel proprietary assay can screen combinations BsAbs and checkpoint inhibitors

Vivia Biotech

11.30 Structural Optimization of Bispecific Antibodies for Conditional Immune Activation

  • Understanding how the formats make impact on mechanism of action
  • Controlling the toxicity of immune agonists by design
  • Learning to design better scFv as building blocks

Yoshiko Akamatsu, Senior Principal Research Scientist, Abbvie

12.00
Lunch & Networking

Investigating & Contrasting Innovative Bispecific Constructs

13.30
Avoiding Pitfalls in Format Design – Understanding Why Bispecifics Have Behaved Unexpectedly in the Past to Give a Greater Certainty in Moving into the Clinic in the Future

  • Dale Ludwig CSO, Biologics Technology, Oncology Research, Eli Lilly

Synopsis

  • Analysing the advantages and disadvantages of a variety of bispecific formats
  • Performing a reality check on the hype surrounding bispecifics – addressing the need to improve potency, control immunogenicity risk and enhance developability
  • Key lessons learned from the development and advancement of therapeutic bispecifics in oncology

14.00
Making Room for Two Paratopes on an Fv: Introducing the DutaFab Platform

Synopsis

  • The DutaFab platform delivers fully human dual targeting Fab molecules with two independent paratopes
  • Heavy and light chain both contribute to high affinity target binding for each of the paratopes
  • Binders can be mixed and matched and reformatted into antibody formats as desired
  • This creates novel bispecifics structurally essentially indistinguishable from a standard monospecific Fab or antibody
  • We introduce the platform technology and discuss applications

14.15
Panel Discussion: Investigating Comparisons Between Formats – Lessons Learned that will Inform Future Format Design

  • Robert Mabry Senior Director, Protein Sciences & Antibody Technology, Jounce
  • Stan Blein Senior Director & Head, Antibody Engineering Innovation & Development, Glenmark
  • Marlon Hinner Group Leader, In Vitro Display, Roche

Synopsis

  • Head to head comparisons investigating why certain arrangements of domains are more efficacious than others in addressing the same targets
  • Investigating how in vitro performance compares to in vivo performance for the different formats currently available
  • Understanding which formats and approaches can successfully meet the criteria required for manufacturability

14.45
Afternoon Refreshments & Networking

Improving the Developability of Bispecifics

15.15
Engineered Fab Domains Promote Efficient Production of Bispecific Antibodies in a Single Cell

Synopsis

  • Single cell process simplifies bispecific antibody production compared to established assembly process from two component antibodies
  • Molecular insights into how engineered Fab domains drive orthogonal pairing of cognate light and heavy chains
  • More complex characterization of single cell bispecific antibody overcome with high resolution analytics
  • Single cell process translates to stable cell line development, a key step for clinical development

15.45
Site-Specific Bioconjugation Approaches for the Preparation of Novel Bispecific Antibody Platforms

Synopsis

  • Chemical crosslinking techniques can be used to rapidly prepare highly uniform bispecific antibody constructs, opening up an opportunity to screen for optimal antigen binding pairs
  • Proximity-based sortase ligation can be used to site-specifically modify bispecific antibodies with chemical moieties (e.g. imaging agents, PEG) in a modular fashion, during standard protein purification protocols

16.15
Developability & Analytical Characterization to Enable the Optimal Selection of Bispecific Antibodies

Synopsis

  • Analytical characterization of developability attributes of bispecific antibodies during discovery
  • Selection of highly developable lead molecules with minimum downstream issues
  • Key learning for bispecific antibody production, purification, and characterization

16.45
Chair’s Closing Remarks