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,



COBRA: A Novel Conditionally Active Bispecific Antibody that Regresses Established Solid Tumors in Mice

• We have designed a multivalent sdAb-diabody fusion which converts into a highly potent bispecific redirected T-cell therapeutic upon proteolytic activation
• In vitro assays demonstrate protease dependent linker cleavage increases potency of T cell-mediated killing 200-fold, yielding a therapeutic with sub-picomolar potency
• Administration of MVC-101 in mice with established xenografts resulted in protease cleavage dependent T-cell mediated tumor regressions in multiple tumor models
• MVC-101 has extended half-life in vivo upon administration, and rapid clearance post proteolytic activation, resulting in a therapeutic with improved safety profile over conventional T-cell redirected bispecifics

Danielle Dettling

Director, R&D

Maverick Therapeutics


Solid Tumor Target Selection For Successful Development of BiTE® (Bispecific T Cell Engager) Molecules

• Review case studies of select targets, focused on target expression analysis and preclinical safety
• Discuss target characteristics that impact potential for successful development

Elizabeth Pham




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


Ligand's OmniAb® therapeutic antibody platforms produce highly diversified, fully human antibody repertoires optimized in vivo for manufacturability, therapeutic efficacy and reduced immunogenicity - Naturally optimized human
antibodies®. The single-license OmniAb offering is the industry's only with three species and multiple genetic backgrounds - 3 species, 1 license™

Christel Iffland, VP, Antibody Technologies, Ligand




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


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

Robert Doornbos, Senior Director, Product Development, Merus







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




A Translational Quantitative Systems
Pharmacology Model for CD3 Bispecific Molecules: Application to Quantify T-Cell-Mediated Tumor Cell Killing by P-cadherin LP DART

• A translational quantitative systems pharmacology (QSP) model is proposed for CD3 bispecific molecules capable of predicting trimolecular complex (trimer) concentration between drug, T-cell and tumor cell, and linking it to tumor cell killing.
• The model was used to quantify the PK/PD relationship of a CD3 bispecific targeting P-cadherin (PF-06671008). It describes disposition of PF-06671008 in the central
compartment and tumor in mouse xenograft models, including binding to target and T-cells in the tumor to form the trimer. The model incorporates T-cell distribution
to the tumor, proliferation and contraction.
• The model was translated to the clinic and used to predict the disposition of PF-06671008 in patients, including the
impact of binding to soluble P-cadherin. The model was also used to predict clinical efficacy of PF-06671008 and to investigate sensitive factors which impact efficacy.

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














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, Director of Research & Development, Mythic Therapeutics 


Lunch & Networking 

Pioneering Novel Discovery Approaches

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

Enhancing the Developability of Bispecifics

1:30 Screening for Format - Combinatorial High-Throughput Generation 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

• Enabling technology on automated platform for "screening in final format"

Stefan Dengl, Principle Scientist Large Molecule Research, Roche


2.00 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



2:30 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


1.30 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



2.00 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





2.30 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

Emmanuel Normant, Vice President, Preclinical Sciences, TG Therapeutics

Raphael Clynes, VP, Translational Biology, Xencor

Paul Moore, VP, Cell Biology & Immunity, MacroGenics



1.30 Developability of Bispecific Anitbodies

  • 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




2.00 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

Nathan Higginson-Scott, Senior Director, Protein Technologies, Pandion Therapeutic

Christian Cimander, Senior Director, Team Lead, CMC, Genmab


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.

Utilizing Novel Approaches to Target Disease More Effectively


Codon Usage & Genetic Disease: Using Big Data for More Accurate Disease Prediction

• Discussing the role of synonymous mutations in disease and codon optimized therapeutics
• Introduction of a new database that includes genomic codon, codon-pair and dinucleotide statistics of all organisms with publicly available sequenced genome
• Outline of a novel, accurate in silico tool for prediction of disease-causing synonymous and non-synonymous mutations

Chava Kimchi-Sarfaty

Deputy Associate Director, OTAT, CBER


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

Director, Pharmacokinetics



Gerry Rowse

Director, Toxicology



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

John Burke

President , CEO & Co-Founder

Applied BioMath


Networking Drinks Reception