Antibody Therapeutics Xchange Europe
Target Selection
Finding the best targets and binder combination for bi- or multispecific antibodies
- The use of standard therapeutic antibodies created with conventional lead generation processes have reached their limitations. New target combinations, exploiting rare epitopes or identifying novel bispecific combinations in different antibody formats are urgently needed to find novel applications in various disease settings.
- How do we best select new target (and epitope) combinations that are biologically meaningful and hold promise to tackle novel disease biology?
- How can we generate maximal binder and antibody format diversity to identify highly differentiated biologics?
- What are our experiences and learnings from the use of novel high-throughput technologies and combinatorial platforms to rapidly generate bispecific antibody combinations in differing formats that offer tailored solutions and novel mode-of-actions to address challenging biology
MorphoSys
- Is this class of targets feasibly addressable or purely aspirational?
- What are the notable advances/inroads?
- Are there particular challenges and limitations to the ‘TCR mimic’ antibody approach?
Head, Antibody Research
Immunocore
How to select targets for immunotherapy combinations
- Immunotherapy targeting PD-1/PD-L1 or CTLA-4 has shown impressive results in various cancer indications; however, only a subset of patients respond to single agent therapy.
- Combination immunotherapy presents an opportunity for improving responses and outcomes for cancer patients.
- Currently, 1000s of combination trials are ongoing.
- The development of immunotherapy combinations faces a number of challenges, including selection and validation of targets
Project & Portfolio Director
Symphogen
11:50am – 12:20pm
1-2-1 Meetings
11:50am – 12:20pm
1-2-1 Meetings
4:50pm – 4:55pm
Closing Address
Lead Identification
Harnessing single B cell sorting technologies for lead identification
- What are the pros and cons of these technologies?
- What are the benefits of full diversity understanding vs early detailed functional data?
- Can B cell-based antibody discovery platforms claim to retain the natural VH/VL combination and enable rapid progression into preclinical development or does B cell derived mAbs also required engineering to be of drug quality?
Vice President, Biotherapeutic Discovery
Lundbeck
Allan Jensen is an expert in discovery and preclinical development of antibody-based drugs and has several years of experience from various positions in the biotech and pharmaceutical industry. Allan holds M.Sc. and Ph.D. degrees in Molecular Biology for University of Aarhus. He entered the field of antibody discovery at Symphogen A/S almost two decades ago, continued his career at Pfizer and joined Lundbeck as Senior Director, with responsibility for Biotherapeutic discovery where he is now Vice President of the group. He has provided significant scientific input to technologies for antibody discovery and bringing drug candidates into the clinic.
- What is physiologically relevant data?
- How do you measure binding in complex matrices?
- How does temperature affect binding?
- Does purifying your samples affect binding?
Head of Operational Business – Europe
Sapidyne Instruments
Frank Hamacher is a Biochemist and worked in Cancer Research at the “Institute of Pathology” at the Charite in Berlin and in the “Laboratory of Immunological and Molecular Cancer Research” in Salzburg/Austria, with focus on Chronic Lymphocytic Leukemia, Anaplastic Large Cell Lymphoma and Breast Cancer, detecting
Biomarkers for Cancer Therapy. In 2014 he joined Sapidyne Instruments to run the
European Business regarding Customer Service, Advice and Supervision. With the KinExA-Technology from Sapidyne Instruments you can measure Affinity and Kinetics of Proteins under natural conditions and directly in Cell systems.
We leveraged the Berkeley Lights Beacon® Platform to identify a set of diverse Anti-PD-L1 Antibodies by Single Plasma B Cell Cloning. We compared this method to that of a standard hybridoma approach. We evaluated over 30,000 single B cells and over 14,000 hybridoma clones for the ability to bind human PD-L1 expressed on cells and block binding of PD-L1 to PD1. This study resulted in identification of 19 blocking antibodies by B cell cloning with diverse sequences and a sub-set of these antibodies had comparable or better potency and sub-nM affinity compared to benchmark anti-PD-L1 antibodies. The hybridoma antibodies also had blocking activity and represented broader epitope coverage but fewer of the antibodies had functional potency or affinity comparable to benchmark antibodies.
1:35pm – 2:35pm
- Is extensive lead optimization generally required and acceptable?
- What attributes/qualities are generally easy and worth optimizing for lead antibody selection?
- Are computational prediction tools, AI/ML algorithms better than e.g. library-based screening for antibody optimization?
- What are the current best applications for natural repertoire data in therapeutic lead optimization?
- Are state-of-the-art antibody optimization technologies (computational methods, bioinformatics, screening etc.) paving the way for refurbishing failed candidates?
Principal Scientist, Biotherapeutic Discovery Lundbeck
Berit Olsen Krogh has a background in molecular biology, protein engineering and structure-function mapping. Started working on therapeutic antibodies more than 12 years ago, initially for humanization of rodent and rabbit antibodies. Responsibilities expanded to general antibody discovery, engineering, expression and production cell line development. Currently working on developing antibody-based therapeutics for treatment of neurodegenerative diseases and other CNS disorders at Lundbeck. Continue to focus on antibody discovery, functional characterization and developability profiling. Main responsibilities cover, design and implementation of antibody discovery and engineering campaigns. Key activities also include maturing Lundbeck’s internal antibody technology platforms and developing network of external technology partners.
2:40pm – 3:10pm
1-2-1 Meetings
3:10pm – 3:40pm
1-2-1 Meetings
3:45pm – 4:45pm
- Advantages, limitations and biases of both methods (WT vs. Transgenic animals, species, immunization strategy, isolations vs. fusions, access to immune repertoire)
- Moving function forward in Ab discovery: advantages and limitations using hybridoma supernatant vs. single B cells
- Defining a “hit” – how stringency in setting cutoffs can create bias in hit selection
- How to maximize epitope and sequence diversity during screening
Senior Director Biologics
ChemPartner
Shireen S. Khan, PhD is a Senior Director of Biologics at ChemPartner in South San Francisco, where she leads a Biologics group that has expanded ChemPartner’s capabilities into single B cell cloning on the Beacon platform. She also leads multiple therapeutic antibody discovery programs for biotech and pharmaceutical companies. Prior to ChemPartner, Shireen led the cell and functional biology group at XOMA and advanced several therapeutic candidates through in vitro and in vivo efficacy studies. She completed her PhD in Biology at the University of California, San Diego and Post-doctoral training at DNAX studying cell cycle checkpoints that fail in cancer.
4:50pm – 4:55pm
ClosingAddress
Antibody Optimisation
- Affinity: nM or pM?
- Manufacturing sequence liabilities: risk or reality?
- Charge patches: asymmetric or balanced?
- T-cell epitopes: germline or non-germline, FW or CDR?
Senior Director, BioMedicine Design
Pfizer
Orla Cunnigham is Senior Director of Pfizer’s BioMedicine Design antibody discovery and optimization group based in Dublin. Her team use advanced protein engineering technology platforms to discover, evolve and optimize therapeutic antibodies, supporting programs across Pfizer’s diverse therapeutic research units based in the US including oncology, immunology, cardiovascular & rare diseases. Orla obtained her PhD in Biochemistry from Trinity College Dublin and followed this with postdoctoral research in cancer cell biology at the institute for molecular oncology in Milan. Orla has co-authored numerous publications and patents in the field of therapeutic antibody engineering.
- How to optimize antibody sequence without introducing unnatural mutations?
- How to thoroughly explore natural antibody sequence space around your lead?
- Humanizing and optimizing your lead at the same time – pitfalls?
- How do you exclude potential developability dipeptide motifs from your library?
Chief Scientific Officer, Biopharma
Twist Biopharma, a division of Twist Bioscience
Aaron is Chief Scientific Officer of the Biopharma Vertical at Twist Bioscience. Prior to Twist, he served as Chief Scientific Officer of LakePharma, leading the California Antibody Center, which discovers novel antibody therapeutics for its clients. He also oversaw all discovery research functions both as Vice President of Protein Sciences at Surrozen, and previously, as Vice President of Research at Sutro Biopharma, Inc. He also held director level positions at both Oncomed and Dyax Corp.
New mAbs or agents with other structures have revolutionized treatment options for several diseases and malignancies in the past few years, and more are currently being evaluated in the clinic. The development of new therapeutics comes with a series of challenges and questions, of which one is the risk for unwanted immunogenicity which can lead to decreased efficacy and safety concerns.
Today, both in silico and in vitro preclinical tools are available to identify early on therapeutic candidates with a high immunogenicity risk potential. Additionally, certain tools can be used to mitigate the immunogenicity potential, and thus improve and accelerate therapeutic drug development and reduce the number of clinical failures.
1:35pm – 2:35pm
- Starting with the end in mind: liabilities with the highest impact on the commercial product
- Identifying the most predictive methods and translation to CMC
- Developability platform vs bespoke methods
- Balancing speed vs quality in lead identification
Head of Molecular Design and Engineering
GlaxoSmithKline
Emma Harding is Director of the Molecular Design and Engineering group within Biopharm Discovery at GSK. Her team focus on understanding quality attributes of molecules such that we can improve the developability of leads within the Discovery process, by a combination of protein engineering, molecular biophysics and analytical characterisation. Emma received her PhD in protein biophysics from the University of Nottingham, followed by a postdoc at the Technische Universität Munich. She has worked at the interface of Discovery and Development at GSK for over 10 years, utilising the expertise across the organisation to develop higher quality therapeutics.
2:40pm – 3:10pm
1-2-1 Meetings
3:10pm – 3:40pm
1-2-1 Meetings
3:45pm – 4:45pm
- Which technologies and assays do you consider crucial to identify and quantify mispaired species?
- Which methods would be appropriate to tackle more difficult mispaired variants (like isobaric mispairings)?
- Which methods are most appropriate to analyze mispairing during the course of Discovery and Optimization and which techniques are superior in later stages of the value chain (CMC Development, Process Characterization, and Control Strategy)
- Which strategy do you consider most appropriate to confirm simultaneous binding of multiple targets, either located on different cells (trans) or on one cell (cis)?
Lab Head, Mass Spectrometry
Sanofi
Soraya Hölper joined Sanofi in 2017 as a Lab Head for Mass Spectrometry. She is acquainted with developability and analysis of complex therapeutic antibodies within the Biologics Research division. Before joining Sanofi, Soraya was responsible for the establishment and maintenance of the mass spectrometry platform at the Institute of Biochemistry II in Frankfurt am Main. She holds a diploma degree in biochemistry from the Goethe University of Frankfurt am Main and did her Ph.D. at the Max-Planck-Institute for Heart and Lung Research in Bad Nauheim in the Biomolecular Mass Spectrometry division.
4:50pm – 4:55pm
ClosingAddress
Alternative Formats
- Does size matter?
- What are the opportunities and limitations of using single domains compared to conventional mAbs?
- How many targets can you hit with one molecule?
- What are the challenges of manufacturing single domain antibodies?
Senior Director, Early Discovery
Crescendo Biologics
Colette joined Crescendo Biologics in 2012, when the science team was just six people. She is now Senior Director, Early Discovery, leading activities in Crescendo’s Humabody discovery pipeline and also manages the proprietary mouse platform. Colette was previously at MedImmune in the department of Antibody Discovery and Protein Engineering.
Colette graduated from the University of Manchester (BSc) and University of Leicester (MSc) and obtained her PhD in Developmental Biology from the University of London. Her post-doctoral research included studies of B cell development, epigenetic regulation of VDJ recombination and analysis of antibody repertoires.
- Why immunogenicity can be assessed early on? When is it considered as a risk?
- How can immunogenicity be assessed?
- What are the strengths and weaknesses of the different approaches (in silico versus in vitro)? Which types of assays have been the most reliable?
- What are some common challenges and how can they be overcome? How do these data correlate to the clinical outcome?
- What are the regulatory bodies advising and how do they interpret the data?
Founder & Chief Technology Officer
ImmunXperts
Sofie has over 20 years of experience in the field of immunogenicity assessment (vaccines and biotherapeutics). She has extensive hands-on lab experience and has managed and coached several In Vitro teams over the last decade. From 2008 till 2013 she was Head of the In Vitro Immunogenicity group at AlgoNomics (Ghent, Belgium) and Lonza Applied Protein Services (Cambridge, UK). Prior to that, she worked at Innogenetics, Belgium for over 15 years.
- Fc engineering is almost becoming as important as antibody engineering for therapeutic antibodies
- What determines the choice of Fc engineering technology for therapeutic efficacy?
- What impact does Fc engineering have on antibody half life?
- What are the implications of combining Fc engineering with multispecific platforms?
- What impact does Fc engineering have on developability?
Senior Scientist, Protein Sciences
Agenus
Mark Bushell is a Senior Scientist at Agenus where he leads platform development initiatives to improve in-house antibody optimisation processes. Following degrees in Chemistry and Biochemistry Mark has experience across many fields working in both academia and industry on platform and process development. As antibody research continually delivers innovations that promise greater therapeutic efficacy Mark is passionate about how protein engineering can be used to ensure the next generation of therapeutic antibodies retain the biophysical properties required for manufacturing and developability. Only when both biology and developability are successful will new antibody-based therapeutics deliver long-term benefits for patients.
2:40pm – 3:10pm
1-2-1 Meetings
3:10pm – 3:40pm
1-2-1 Meetings
3:45pm – 4:45pm
- Electrostatic, hydrophobic or sterically favourable mutations for chain heterodimerisation… Which method is preferable?
- Are there manufacturing issues to be aware of with different pairing strategy for both research and CMC?
- Is the heterodimer bispecific IgG format still favoured over alternative formats?
Director, Discovery
NovalGen
David graduated from University of Manchester with a BSc and MRes in Pharmacology before conducting a PhD in Molecular Biology at Imperial College. From there David joined GSK and began working in biopharmaceutical discovery, with a particular focus on bispecific antibodies. Building on this experience, he moved to Crescendo Biologics in Cambridge to work with multispecific Humabodies. After spending nearly 10 years gaining extensive experience in antibody engineering, leading therapeutic discovery programmes and leading academic collaborations, in autumn 2019 David joined UCL spin out NovalGen as Director of Discovery, leading a team to develop novel bispecific antibody therapeutics.
4:50pm – 4:55pm
Closing Address
Targeted Therapies
- Balance affinities of target and effector arm
- Co-targeting of effector targets
- Properties of new effector modules
Group Leader, Global Biotherapeutics
Sanofi
Ercole Rao received his PhD in Molecular Biology from the University of Heidelberg. He has 17 years of industrial experience, 13 thereof spent in antibody discovery, research and development. Ercole heads a group for Protein Engineering at Sanofi with a focus on Multispecific Antibody Technologies. Since 2009 Ercole’s team moved 3 bispecific antibodies into clinical development.
- What strategies are being used to perform single cell isolation, screening and sequencing?
- How to perform pairing of heavy and light chains?
- How to validate the functionally relevant leads identified?
- How to interrogate the lineage of leads?
Director, Business Development
Rapid Novor
Anthony has been heading the business development at Rapid Novor for nearly 4 years, merging his previous 8 years of experience in the business roles with a strong passion for biomedical research, stemming from his training in biomedical engineering. His current efforts are focused on the growth of the REpAb™and NovorIg™ platforms with pharmaceutical and biotech companies globally. His partnerships are focused on using REpAb in patients or animal models to sequence monoclonal antibodies from polyclonal sera, as well as immune system profiling using NovorIg, the team’s NGS based analysis to monitor the relative quantity of specific antibodies over time. Anthony’s a maker and in his spare time takes advantage of the Toronto HackLab to do biological research and other engineering projects.
- Targeting, activation by environmental triggers, cytokine engineering, … what are the most promising approaches out there?
- Maximizing efficacy or safety: which way to go?
- Several compounds, which focus on IL2, are already in the clinic. What’s next?
Head, Large Molecule Research
Roche
Stefan Weigand, has been with Roche since 2005. He is currently Head of Large Molecule Research at Roche pRED, responsible for Roche’s industry-leading efforts in biologics from concept to clinic. Prior to taking on this role in 2015, Stefan acted as Head of Biochemical and Analytical Research for Biologics and has held several roles with increasing responsibility in Discovery Oncology and External Innovation.
Before joining Roche, Stefan worked in pre-clinical research at Bayer Health Care. Stefan is a chemist by training (Universities of Würzburg and Göttingen) and has completed his postdoctoral studies at Stanford University, California.
2:40pm – 3:10pm
1-2-1 Meetings
3:10pm – 3:40pm
1-2-1 Meetings
3:50pm – 4:55pm
Closing Address