Chair’s Opening Remarks

Jonah Rainey,


Gritstone Oncology

Enhancing the Selectivity of Bispecifics in Solid & Liquid Tumor Indications


Designing T-cell Engagers for Better Therapeutic Windows

• Sequence-based antibody discovery using transgenic human IgG rodents
• Engineering, optimizing and selecting multi-specific leads for desired biology
• Considerations in selecting the efficacy and potency of T-cell engagers for liquid and solid tumor targets
• Designing the next generation of safer therapeutic bi- and multi-specific T-cell engagers

Omid Vafa,

Chief Business Officer,



Designing T-cell Engagers for Better Therapeutic Windows

• Sequence-based antibody discovery using transgenic human IgG rodents
• Engineering, optimizing and selecting multi-specific leads for desired biology
• Considerations in selecting the efficacy and potency of T-cell engagers for liquid and solid tumor targets
• Designing the next generation of safer therapeutic bi- and multi-specific T-cell engagers

Danielle Dettling

Director, R&D

Maverick Therapeutics


Panel Discussion: Examining & Interpreting Failures in the Field to Enhance Future Development

In order to succeed in the field, it’s as important to learn about failures than successes. Bispecific therapeutics have been around for decades and over 100 formats currently exist, so why aren’t there more approved bispecifics? Examining the reasons behind failures will help to move forward with more clarity. This panel discussion will bring together perspectives from organizations who have experienced failures in the development of bispecifics to speak candidly about the underlying issues behind the failure and lessons learnt that can be implemented moving forward. Topics to be discussed include:

• What leads to a program being pulled from the clinic?
• What are early warning signs that have proved good predictors of failures in scale up?
• At which stage are failures typically occurring and why?
• Investigating the relative roles of factors such as manufacturability, toxicity and selectivity

Tariq Ghayur,

Senior Research Fellow,



Eugene Zhukovsky,


Biomunex Pharmaceuticals


Chris Mehlin,

Director, Therapeutic Proteins. Senior Staff Scientist,

Fred Hutchinson Cancer Research Center


Morning Refreshments & Speed Networking

Optimizing High-Throughput Screening to Enhance Bispecific Discovery

Translational & Clinical
Building & Executing a Robust Preclinical Strategy

Manufacturing & CMC
Understanding the Unique Analytical Challenges Bispecifics Pose


Bispecific Target Discovery by High Throughput Functional Screening of Hundreds of Combinations of Target Pairs

• Technology platform to discover novel target pairs by unbiased functional screening with large, diverse, combinatorial panels of bispecific antibodies

• Platform combines 3 key technologies: antibody discovery, a novel bispecific screening format and high content high throughput screening

• The platform is applicable to any disease area

• Example of discovery of novel obligate target pairs will be described for autoimmunity, fibrosis and immuno-oncology

Helene Finney, Head, Bispecific Target Discovery, UCB




Bringing the Tumor-Directed CTLA-4 x OX40 Bispecific Antibody, ATOR-1015, Into the Clinic

• ATOR-1015 is a CTLA-4 x OX40 bispecific antibody developed for tumor-directed immunotherapy

• ATOR-1015 binds both targets simultaneously, promoting cell-cell interactions expected to enhance the immune activation

• The mode of action is a combination of regulatory T cell (Treg) depletion and effector T cell activation
• ATOR-1015 has anti-tumor effects in several syngeneic tumor models in mice and improves the response to anti-PD-1 treatment

• A first-in-human phase 1 study has started in patients with advanced solid tumors (NCT03782467)

Tina Furebring, SVP, R&D, Alligator Bioscience


Investigating a Novel Computationally & Structurally Designed Methodology to Generate Bispecifics

• Understanding a new methodology to generate bispecifics using G4 unidirectional drivers
• Creating mutations on the CH3 domain and using them as bait to fish out naturally occurring bispecifics from the hybridoma pool
• Understanding the advantages of this approach, including the significant time savings from screening from the hybridoma pool directly into a bispecific format

Igor D’Angelo, Senior Research Scientist, Molecular Engineering, Amgen







Screening in Final Format - Combinatorial High-Throughput Generation & Functional Screening of Bispecific Antibodies in Different Formats

• Protein engineering: robust generation of bispecific antibodies by controlled heavy-chain exchange

• Combinatorial bispecific diversity: generation of binder-format matrices

• Format defines function: screening of bispecific matrices identifies formats with desired function

• Outlook: expansion of an automated HTP bispecific platform

Stefan Dengl, Principle Scientist Large Molecule Research, Roche


Alison Betts, Associate Research Fellow, Translational Modeling & Simulation, Pfizer













Establishing Effective Cell Line Development & Analytical Approaches to Support the Clinical Development of Bispecific Therapeutics

• Insights from overseeing the whole CMC and manufacturing trajectory – understanding the challenges faced at each stage

• Understanding how to approach cell line development in the bispecific space

• Case study: An in-depth insight into the CMC approaches that support the development of a clinical bispecific candidate

Robert Doornbos, Senior Director, Product Development, Merus


Lunch & Networking 

Pioneering Novel Discovery Approaches

Insights into the Translatability &
Clinical Development of CD47-Targeting Bispecifics

Enhancing the Developability of Bispecifics

1.45 Facile Production of Bispecific Antibodies for High-Throughput Screening of Antibody Pairs & Personalized Therapy

• Photoreactive antibody binding domains (pAbBDs) can be used for the rapid and site-specific labeling of nearly any ‘off-the-shelf’ IgG

• Bispecific antibodies can be formed from nearly any two full-length IgG, using pAbBDs, for rapid testing of antibody combinations.

• Anti-tumor antibodies collected from serum can be rapidly converted into T cell-redirecting autoantibodies (TRAAbs)

Andrew Tsourkas, Professor, Bioengineering, University of Pennsylvania

2:15 Designing Bi- & Multi-Specific CD3/X Molecules to Match Biology & Clinical Unmet Needs

• Technical challenges for designing bi-/multi-specific biologics have been (or can be) solved

• Key challenges now are to design the right therapeutic molecules to match biology/clinical unmet needs

• Key aspects to consider are: (i) the right target pairs; (ii) position of variable domains, valency of each specificity & linker designs, if needed; and (iii) ensuring that the final therapeutic candidate has the right drug-like and PK profiles

• Some examples of above will be provided

Tariq Ghayur, Senior Research Fellow, Abbvie

2.45 Panel Discussion: Investigating Novel Bispecific Designs to Overcome Biological Challenges

• Matching specific biological application to format design

• Investigating approaches to modulate half-life and the effects of this modulation on immunogenicity, efficacy and safety

• Gaining insights from novel format designs and discovery work

Eugene Zhukovsky, CSO, Biomunex Pharmaceuticals

Andrew Tsourkas, Professor, Bioengineering, University of Pennsylvania

Tariq Ghayur, Senior Research Fellow, AbbVie


1.45 Enhancing the Specificity of CD47-Targeting to Improve the Therapeutic Window

• Investigating the rationale behind targeting CD47

• Producing a potent and targeted anti-tumour activity while mitigating against toxicities associated with CD47 targeting

• Improving translatability by utilising in vivo models and
patient samples

Emmanuel Normant, Vice President, Preclinical Sciences, TG Therapeutics



2.15 Targeting CD47 with a Bispecific Molecule for Superior Efficacy & Better Safety Profile

• Designed a bispecific antibody to prevent anti-CD47 offtissue toxicity by selectively binding to cancer cells

• The bispecific antibody displayed synergy between two targeted pathways related to innate and adaptive immunity, respectively
• Besides blood malignancies, this molecule has potential in solid tumors as well

Junjian Liu, VP, Head of Drug Discovery & Preclinical Development, Innovent Biologics





2.45 Panel Discussion: Enhancing the Translatability & Predictability of Animal Models

• Contrasting in vivo modelling approaches to extract useful data to inform clinical development

• Are in vivo efficacy and safety models sufficient to get good predictions of therapeutic windows?

• Back-translating clinical experience to avoid toxicities in the future

Tina Furebring, SVP, R&D, Alligator Bioscience

Emmanuel Normant, Vice President, Preclinical Sciences, TG Therapeutics

Alison Betts, Associate Research Fellow, Translational Modeling & Simulation, Pfizer



1.45 Understanding the Developability Issues Behind Bispecific Failures

• Contrasting developability issues encountered by a range of bispecific formats

• Understanding developability attributes that can be early predictors of failure

• Investigating a case study highlighting challenges encountered in the development of a bispecific

Nimish Gera, Co-Founder, Director of Research & Development, Mythic Therapeutics




2.15 Developability of Bispecific Antibodies

• In-silico predictions to assess developability

• In-depth characterization of side products for bispecific antibodies

• Functional assays for lead characterization

Martin Bader, Head of Biochemical & Analytical Research, Roche








2.45 Panel Discussion: Implementing Strategies to Improve the Developability of Bispecifics

• Understanding the data that needs to be generated to move projects from discovery to early development

• Extracting valuable developability insights from clinical experience – how can we streamline the development of the next generation of bispecifics?

• Bioprocessing innovations to bring down technical hurdles holding back progress in the space

Martin Bader, Head of Biochemical & Analytical Research, Roche

Igor D’Angelo, Senior Research Scientist, Molecular Engineering, Amgen

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


Afternoon Refreshments & Scientific Poster Session

The scientific poster session is an ideal opportunity to communicate your new results and expertise to a niche audience of industry experts, get feedback from peers and colleagues in the industry and learn how others in the field have been tackling similar challenges.

Pioneering Quantitative Models to Predict Optimal Bispecific Properties

Chaired by: John Burke President, CEO & Co-Founder Applied BioMath


Utilizing QSP Modeling to Inform Clinical and Nonclinical Development of Zymeworks’ Azymetric™ Biparatopic Platforms: Pharmacokinetic/Pharmacodynamic Modeling and Therapeutic Index Estimation

• Inclusion of biparatopic binding stoichiometry drives more precise fit of PK data in cynos and humans

• Development of novel pharmacodynamic parameter to evaluate effective of dose concentration and regimen on efficacy

• Estimated delivery of toxin to four compartments: tumor, on-target organ toxicity and off-target toxicities associated with free toxin and FcGammaR2a binding of the antibody

• Therapeutic index estimation with different doses and dose frequencies

Rupert Davies

Senior Scientist, Preclinical Development



Gerry Rowse,

Director, Toxicology & Pharmacokinetics,



Model-Based Approach to Design Bi-Specific Modalities in Early Discovery

• Bispecific antibodies are an attractive modality to modulate multiple targets in a disease indication. Each antigen may exhibit similar or different kinetic values like half-life, internalization rates, and expression rates. Target coverage for each antigen may also differ or be similar

• Understanding your drug targets is critical to building an appropriate drug that specifically binds to and elicits the magnitude and duration of response needed for a particular indication

• Here we used a tiered model-based approach to first determine feasibility of a bispecific antibody to appropriately cover multiple antigen pairs

• Once feasibility was assessed, further modeling was performed to determine ideal affinity ranges for each target in bispecific format at the site of action. Sensitivity analysis was performed to understand each parameter and its impact on predicted target coverage

• This approach guided teams for informed antibody design, prioritization of experiments, and triaging of challenging
antigen pairs

Jennifer Fretland

Head, Drug Metabolism & Pharmacokinetics



The Next Generation of T-Cell Redirecting Antibodies

• Harnessing the immune system has revolutionized cancer treatment

• In particular redirected T-cells can kill tumor cells in therapeutically useful ways

• However, off-target toxicity and lack of sufficient Ag limit the therapeutic potential of these approaches

• Revitope is developing two-component systems composed of conditionally activated T cell Engaging Antibody Circuits

(TEAC) that initiate and focus cytotoxic immunity accurately on the tumor

• The core idea of TEAC is to split the anti-CD3 paratope of a bi-specific antibody to separately target each half-paratope to the tumor and only permit reconstitution after protease cleavage of the stabilizing dummy domains.

• TEAC can be tumor-targeted with one or two different solid-tumor antigens (requirement for two antigens (an “AND” gate) that may enable greater tumor-specificity

• The discussion will cover protein engineering considerations, activity measurements and the use of quantitative systems pharmacology modeling approaches aid mechanistic understanding

Werner Meier


Revitope Oncology


Chair’s Closing Remarks

Jonah Rainey


Gritstone Oncology