11th Annual

Developability of Bispecific Antibodies

Connecting Platforms, Formats, Engineering and Manufacturing for Multi-Specifics

January 17 - 18, 2022 ALL TIMES PST

The Developability of Bispecific Antibodies conference is a continuation of this successful series at PepTalk and will examine the vastly expanding repertoire of bispecific antibody constructs to identify and select molecules early in the development process that have favorable drug-like properties including half-life, pk/pd, immunogenicity, and stability, while also being more easily manufactured. This meeting will span from discovery and engineering all the way through clinical development while introducing developability concepts and parameters earlier in the process to foster greater overall success in the quest to develop a wide array of new multi-specific antibodies with greater functionality and efficacy.

Sunday, January 16

4:00 pm Conference Registration Open (Sapphire West Foyer)

Monday, January 17

7:00 am Registration and Morning Coffee (Sapphire West Foyer)


Session Room: Sapphire L

9:00 am Organizer's Welcome Remarks

Christina C. Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute


Developability of Bispecific Antibodies

Paul Parren, PhD, Executive Vice President, Lava Therapeutics; Professor, Leiden University Medical Center

Dual-targeting concepts enabled by bispecific antibodies (bsAbs) hold great therapeutic promise, but translation of these concepts into treatments has proved challenging. Solutions for technical difficulties in both discovery and developability of bsAbs, which hampered the field for many years, have been sought. This presentation provides an overview of the research that led to the development of the DuoBody technology which stood at the basis for the recently approved bsAb amivantamab.

9:40 am

Developability of Complex Multispecifics

Sagar V. Kathuria, PhD, Senior Principal Scientist, Large Molecule Research, Sanofi

Evolving analytics for developability assessment of highly engineered antibodies. With the advent of highly engineered antibodies in the therapeutic landscape, analytical methods for developability assessment have had to keep pace. The unique properties of multispecific antibodies and the challenges associated with their assessment will be discussed.

10:10 am

Design Meets Biology – Engineering a PD-1/CTLA-4 Monovalent Bispecific Antibody to Improve Both Safety and Efficacy

Yariv Mazor, PhD, Senior Director, Biologics Engineering, AstraZeneca

MEDI5752 is a monovalent bispecific IgG1 antibody (DuetMab), targeting the two clinically validated receptors; PD-1 and CTLA-4. The bispecific antibody introduces novel MOAs that may provide an improved therapeutic index when compared to the two monotherapies and mAb combinations. MEDI5752 is currently being clinically evaluated for safety and efficacy.

10:40 am Networking Coffee Break (Sapphire West Foyer)

Trispecific Antibodies – Taking the Concept of Multi-Targeting One Step Further

Ercole Rao, PhD, Group Leader Biologics Research, Engineered Protein Therapeutics, Sanofi Germany GmbH

In the past decade, the dream of designing bispecific antibodies capable of simultaneously engaging two targets has become reality and this modality is considered by many as “the new magic bullet." With more than 100 bispecific antibodies already in clinical development, antibody engineers are working on innovative ways to add even more functionality and specificity to the ever-growing antibody toolbox. We have developed novel tri-specific antibodies, like a triparatopic anti-HIV antibody or a trispecific CD3xCD28xCD38 T cell engager that are currently being evaluated in clinical studies. However, the molecular complexity of such molecules may pose significant challenges for their developability. 

11:30 am

PrecisionGATE: Developing the Next Generation of T Cell Redirecting Technology

Allison Colthart, PhD, Scientist, Revitope Oncology
Josefin Bolik, MS, Global Product Manager - Antibody Platforms, Marketing, Cytiva

The pipeline for antibodies, the largest class of biotherapeutics today, is growing in diversity with variants such as bispecifics, conjugates, or fragments. Platform approaches for purification work well for many monoclonal antibodies (mAbs) on the market but selecting purification schemes can be challenging for antibody variants due to molecular diversity. We’ll discuss how to select affinity resins to achieve selectivity and purification outcomes using established and new ligand innovations.

12:30 pm Enjoy Lunch on Your Own
1:10 pm Session Break


1:45 pm

Chairperson's Remarks

Nimish Gera, PhD, Head, Biologics, Mythic Therapeutics
1:50 pm

Developability Algorithms

Peter M. Tessier, PhD, Albert M. Mattocks Professor, Pharmaceutical Sciences & Chemical Engineering, University of Michigan

We have developed machine learning models for identifying antibodies with optimal combinations of high affinity and drug-like biophysical properties. Our approach combines novel descriptors of antibody molecular features with neural networks to identify Pareto optimal antibody variants with different levels of affinity improvement while minimizing natural trade-offs involving other key properties (e.g., specificity). These methods greatly reduce the required experimentation needed during antibody engineering efforts for co-optimizing multiple antibody properties. 

2:20 pm

Predicting Antibody Developability Profiles through Early Stage Discovery Screening

Laurence Fayadat-Dilman, PhD, Senior Director, Protein Sciences, Merck Research Laboratories

We developed a practical high-throughput developability workflow (100’s-1,000’s of molecules) implemented during the early phase of antibody generation and screening to guide the selection process of the best lead candidates. Mining of our high-quality datasets identified novel patterns and correlations between biophysical assays. These patterns and correlations represent the basis for training deep neural networks and establishing machine learning algorithms for in silico interrogation and prediction of developability profiles.

2:50 pm Find your table and meet the BuzZ Sessions Moderator
3:00 pm BuzZ Sessions with Refreshments (Sapphire Foyer)

PepTalk BuzZ Sessions are focused, stimulating discussions in which delegates discuss important and interesting topics related to upstream protein expression and production through downstream scale-up and manufacturing. This is a moderated discussion with brainstorming and interactive problem-solving between scientists from diverse areas who share a common interest in the discussion topic. Continue to check the event website for detailed discussion topics and moderators.

BuzZ Table 8: In Silico Downstream Process Development

Thiemo Huuk, PhD, Sales Leader, GoSilico, Cytiva
  • Drivers for developing processes in silico 
  • Smart model selection: statistical, mechanistic, or both?
  • Good modeling practices: workflow and best practices
  • Modeling opportunities beyond antibody applications​


3:55 pm

Chairperson's Remarks

Nimish Gera, PhD, Head, Biologics, Mythic Therapeutics
4:00 pm

Brain Delivery of Therapeutic Proteins Using a Novel Fc Fragment Blood-Brain Barrier Transport Vehicle

Mihalis Kariolis, PhD, Senior Scientist, Antibody & Protein Engineering, Denali Therapeutics, Inc.

Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB). We describe the engineering and characterization of a BBB transport vehicle (TV) comprising an engineered Fc fragment that exploits receptor-mediated transcytosis for CNS delivery of biotherapeutics. The TV platform readily accommodates numerous configurations, including bispecific antibodies and protein fusions, yielding a highly modular CNS delivery platform.

4:30 pm

Identification and Evaluation of Antibodies Targeting the Brain Vasculature

Eric V. Shusta, PhD, Howard Curler Distinguished Professor, Chemical & Biological Engineering, University of Wisconsin, Madison

The blood-brain barrier presents a major obstacle to brain drug delivery.  We have developed several different enabling platforms for the identification of antibodies against blood-brain barrier resident receptors that could ultimately be used to ferry drug cargo into the brain.  Here we will describe our recent efforts using new screening paradigms to identify blood-brain barrier targeting antibodies capable of delivering therapeutic payloads to the central nervous system.

5:00 pm

Discovery and Development of Faricimab, a CrossMab Antibody Targeting Both Vascular Endothelial Growth Factor (VEGF-A) and Angiopoietin (Ang)-2, for the Treatment of Retinal Diseases

Christoph Ullmer, PhD, Senior Principal Scientist, pRED Discovery Ophthalmology, F. Hoffmann-La Roche AG

Multiple pathways (e.g., VEGF-A, Ang-2) drive retinal disease by promoting vascular instability; however, current treatments only target VEGF-A. In preclinical studies, faricimab, a bispecific antibody targeting VEGF-A + Ang-2 developed using CrossMab technology, promoted vascular stability. In Phase 3 clinical trials, faricimab resulted in noninferior vision gains, improved anatomic outcomes, and demonstrated potential for extended dosing and comparable safety compared with aflibercept, a VEGF inhibitor, in patients with retinal diseases.

6:00 pm Welcome Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
7:30 pm Close of Day

Tuesday, January 18

8:30 am Registration and Morning Coffee (Sapphire West Foyer)


Session Room: Sapphire L

9:00 am

Chairperson's Remarks

Christina Lingham, Executive Director, Conferences and Fellow, Cambridge Healthtech Institute
9:05 am

From Design to Delivery: How Concepts Impact Manufacturing of Multispecific Antibodies

Stefan R. Schmidt, MBA, PhD, COO & Head, Operations, BioAtrium AG

Multifunctional antibodies represent a major trend in therapeutic modalities. More than 50 different concepts have been established and many of them reached advanced clinical studies. This presentation compares the leading approaches, discusses pros and cons, gives recommendations on design and manufacturing supported by examples from case studies and reviews the current multispecific antibody pipeline in the context of biological function and molecular design.

9:35 am

Bispecific mAb2 Format Harnesses Platform IgG Processes for Rapid and Cost-Effective Drug Development

Mateusz Wydro, PhD, Senior Director, CMC, F-star Therapeutics, Inc.

Typical development and manufacturing of monoclonal antibodies (mAbs) use well established platform methods and processes which evolved over the decades of the biopharmaceutical industry experience. This approach enables a desired combination of high yielding cell lines and rapid development timelines. Due to close similarity to mAbs, in structure and physicochemical properties, F-star’s mAb2 bispecific format presents an ideal format to harness the well-established mAbs platform approaches with minimal optimization, to save time and money in drug development. This talk will explore the application of the platform technologies in manufacturing process development for mAb2 bispecific format.

10:05 am Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
12:00 pm Enjoy Lunch on Your Own
1:10 pm Close of Developability of Bispecific Antibodies