8.30

Chair’s Opening Remarks

Jonah Rainey
VP
Gritstone Oncology

Realizing & Demonstrating the Value of Bispecific Approaches

8.45

Bispecific Antibodies: Evolution & Refinement of their Applications
• The main driver of the success of bispecific Abs is the new biologies they enable
• In addition to well established applications (i.e redirection of immune cells), other applications keep emerging or gaining prevalence (i.e more selective tissue delivery)
• As applications mature, more refined molecules are being developed
• A case study of a more tumor-selective T-cell engager is presented

Diego Ellerman
Principal Scientific Researcher
Genentech

9:15

Exploring the Criteria Under Which Bispecifics are Superior to Antibodies & Antibody Combinations
• Target biology and receptor expression data are key factors in selecting a bispecific versus another therapeutic strategy
• Contribution of cell- and tissue-level antigen expression and bispecific affinity/avidity in driving selectivity and specificity
• Dramatic enhancement of on-target potency through rational selection of antigen, epitope, and bispecific

John Rhoden
Senior Research Scientist
Eli Lilly

9:45

Morning Refreshments & Networking

Discovery

Discovering Approaches to Modify Formats to Enhance Efficacy & Safety

Translational & Clinical

Enhancing Efficacy While Maintaining Safety Throughout Preclinical & Clinical Development

Manufacturing & CMC

Enhancing Process and Analytical Development to Link Discovery Work to Clinical Development

10:30 SMITEs: Putting Some Teeth into BiTEs

• Two bispecific antibodies used in combination can target the coexpression of antigens in tumors while ignoring a single antigen
• Creating a logical AND gate for T cell activation requires each individual molecule to have little/no activity but the combination to be synergistic
• This kind of approach allows the targeting of antigens with wide expression in healthy tissue
• Bispecific architectures are not “Plug and Play” and require optimization for specific antibodies

Chris Mehlin, Director, Therapeutic Proteins. Senior Staff Scientist, Fred Hutchinson Cancer Research Center

 

11:00 Modification of the Bispecific Antibody Platform with an IL-15 Cytokine Crosslinker to Create Trispecific NK Engagers (TRiKEs): Efficacy Against Solid & Liquid Tumors

Lessons learned from the creation of bispecific antibodies engaging NK cells to vastly improve their ability to kill through antibody dependent cell-mediated cytotoxicity (ADCC)

• Investigate a new bioengineered drug whereby the cytokine IL-15 is cross-linked into the BsAb scaffold, creating a new platform whereby NK expansion is maximized while ADCC is promoted

• Discussion of the structure, function, rationale, animal studies, toxicity, and clinical potential of these IL-15 TriKes as they relate to liquid and to solid tumors

•Discussion of effective markers to target against solid tumors

•Discussion of multi-target TriKEs targeting simultaneous tumor markers

Daniel Vallera, Professor, University of Minnesota

11:30 Exploring the Benefits of Targeted, Protease-Sensitive Conditional Bispecifics Through Diverse Examples

• Understanding the unique selectivity that comes from combining conditional and targeted approaches
• Examining molecules that exemplify this idea in a range of indications including:

-Immuno-oncology
-Immunocytokines
-Rheumatoid arthritis

• Investigating potential additional benefits of this approach

Andrew Goodearl, Director, AbbVie

 

 

 

10:30 Optimizing the Clinical Development of Bispecifics in Immuno-Oncology

• Understanding the key clinical challenges encountered in the bispecific space

• Investigating strategies to minimise side effects and maximise therapeutic effects

• Sharing case studies investigating bispecific clinical development in immuno-oncology

Jon Wigginton, CMO & SVP, Clinical Development, MacroGenics

 

 

 

 

 

 

11:00 Insights from the Preclinical & Clinical Development of a Novel CD3-CD123 Bispecific

• Lessons learned from the development of a novel bispecific T cell engager in AML
• Investigating the unique qualities of this bispecific
• Summarising where this will be an advantage to the field in general

Karl Hsu, AVP, Global Head of Early Development Oncology, Sanofi

 

 

 

 

 

 

 

 

 

 

11:30 Preclinical Safety Assessment of Bispecific Antibodies

• Lack of tumor-restricted antigens is the primary barrier to the development of bispecific antibodies for the treatment of solid tumors

•Avidity-based design greatly enhances the selective killing of HER2/CD3 T-cell dependent bispecific antibody

• Preclinical safety evaluation of bispecific antibody should be designed on a case by case base

Sara Santagostino, Scientist-Pathologist, Safety Assessment, Genentech

 

 

 

10:30 Early Stage Process & Product Characterization of Bispecific Antibodies – A Road Map from DNA to FIH

• Best practices for product and process characterization of bispecific antibodies in preparation for FIH filings
• Process and analytical development and characterization: How much is necessary for FIH?
• Structure function relationship in early stage development: How to access and control critical quality attributes early and effectively to stream line process and analytical development
• Examples from multiple bispecific CMC programs based on Genmab’s DuoBody platform will be discussed

Christian Cimander, Senior Director, CMC, Genmab

 

11:00 Incorporation of Bispecific Screens & Robust Analytical Assessment of Drug-Like-Properties at all Stages of Discovery to De-Risk CMC & Pave the Way for Successful Bispecific Development

•Sharing insights into the development of bispecifics to achieve localized immunomodulation to treat autoimmune and inflammatory diseases

Highlighting advantages to incorporation of screening in bispecific format early in the discovery process

Understanding how different tiers of necessary manufacturability assessment can be permeated throughout all stages of discovery for streamlined development and CMC de-risking

Nathan Higginson-Scott, Director, Therapeutic Antibody Technologies, Pandion Therapeutics

 

 

 

11:30 ADAPTIR Bispecifics Platform: Excellent Manufacturability, Extended Half-life and ability to Perform Multiple Novel Mechanisms of Action for Treatment of Multiple Diseases

• ADAPTIR Bispecific platform is capable of generating candidates with unique and different mechanisms of actions for treatment of both cancer and autoimmune diseases
• ADAPTIR bispecific platform has excellent manufacturability characteristics to meet clinical and commercial needs
• ADAPTIR platform has extended half-life to improve on dosing protocols for patient convenience

Jane Gross, CSO, Aptevo Therapeutics

 

 

 

12:00

Lunch & Networking

Mapping Out the Bispecific Landscape

1:00

Review of the Bispecific Landscape

• Insights into the evolving bispecific clinical landscape
• Contrasting bispecific development in solid tumor and haematological indications
• CD3 and beyond: Investigating key bispecific targets
• Evaluating the reasons behind discontinuations – what are the key roadblocks?

Letrishka Anthony

Senior Analyst, Beacon

Hanson Wade

1:30

Mastermind Discussion: Uniting Discovery, Translational, Clinical and Manufacturing Perspectives to Enhance the Future of Bispecific Drug Development

Following the individual tracked elements of the agenda, this session facilitates in-depth discussions between participants from different perspectives in an informal environment. After splitting into small groups, discuss the unique challenges you are facing and collaborate on future strategies to improve the effectiveness of bispecific drug development. Discuss issues such as:

• Reflecting on the unique challenges encountered in the development of bispecifics at every stage
• How can siloes between departments be broken down to improve communication?
• How can outsourcing relationships be improved to ensure internal and external processes and standards are aligned?

2:15

Afternoon Refreshments & Networking

Discovering Effective Checkpoint Inhibitor Combinations

2:45

Design Fitting Bispecifics for Immune Oncology

This presentation will cover various applications of DART and TRIDENT molecules to leverage anti-tumor immunity framed in the context of optimal molecular design. Therapeutic approaches and associated aspects covered in the talk will be:

• Redirected T-cell killing: lessons learned from the clinic and approaches to optimize therapeutic response
• Dual checkpoint blockade: PD-1 x LAG3 and PD-1xCTLA4 – from concept to clinic
• Incorporating immune co-stimulation: tumor conditional CD137 pathway activation including simultaneous checkpoint blockade

Paul Moore
VP, Cell Biology & Immunity,
MacroGenics

3:15

Bispecific Technology for Igniting T Cell Activation through T cell Engagers, Checkpoint Blockade & Cytokines

  • Clinical experience with CD3 engagers
  • Targeting checkpoint blockade and costimulation
  • Potency tuned IL-15 to sustain T cell activation and improve therapeutic index

Raphael Clynes,

VP, Translational Biology,

Xencor

3:45

Chairs’ Closing Remarks

Jonah Rainey

VP

Gritstone Oncology

4:00

Close of Day Two & End of World Bispecific 2019