Antibody Therapeutics Xchange Europe 2019
Target Selection
- What are the implications of low brain bioavailability of antibodies for pharmacological studies and our ability to translate from preclinical models to humans?
- Will enhanced brain exposure by receptor mediated transcytosis provide a solution to this problem and at what price tag?
- Is there an upper limit to the clinical antibodies dose from a biological, regulatory and CMC perspective?
Senior Director 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, and entered the field of antibody discovery at Symphogen A/S almost two decades ago, continued his career at Pfizer and more recently joined Lundbeck as Senior Director, with responsibility for Biotherapeutic discovery. He has provided significant scientific input to technologies for antibody discovery and bringing drug candidates into the clinic.
- Optimal discovery method versus available budget – how do we decide the best path?
- Animal immunizations, natural human antibody repertoire library selection, or synthetic library selection – what are the pros and cons?
- What is the best strategy for choosing the lead candidate selection criteria and at what point should a functional study be integrated – early or later?
- What are the ideal immunization and selection tools? If appropriate cell lines and/or recombinant proteins are not available?
Head of Contract Research
ImmunoPrecise Antibodies
Debby Kruijsen obtained a PhD in immunology at the University of Utrecht, The Netherlands in 2011, studying the role of antibodies in affecting antigen presentation and subsequent Respiratory Syncytial Virus specific T cell activation. In 2012, Debby joined ModiQuest Research, an ImmunoPrecise Antibodies, Ltd. company, as a scientist supervising hybridoma antibody discovery projects. She was promoted in 2013 to Head of Contract Research for ModiQuest Research were she is responsible for the daily management within the CRO and is a member of the business development group.
- How good/predictive are our preclinical models?
- What do we do in situations where there are no target orthologues in the typical animal models used?
- Are advanced in vitro models an alternative to animal models?
- Is it possible to get investigational new drug approval without animal efficacy data?
Vice President Research
Symphogen
Mikkel has more than 10 years’ of experience as scientific leader of oncology and immuno-oncology projects from concept over lead selection through to clinical development.
Major achievements include the discovery and development of six clinical stage programs. He is also the co-author of 35 peer-reviewed papers in the oncology space.
Currently Mikkel is heading the Research Department at Symphogen and is responsible for antibody discovery, in vitro functional screening and mechanisms of action studies.
1:30pm – 2:30pm
2:30pm – 3:00pm
3:00pm – 3:30pm
3:30pm – 3:40pm
3:40pm – 4:10pm
- Well-validated vs new/novel targets? Evolutionary vs revolutionary approach to target selection? Where to find a balance.
- What are the key approaches used to discover novel and disease-relevant targets and does this vary between big pharma and small biotech?
- How important is in-house target validation prior to start of lead discovery?
- How much consideration is given to FTO, IP potential and competitive landscape during the target selection process?
- How important is cross-species homology of target and the likelihood to be able to generate a cross-reactive antibody for preclinical research?
- What is the willingness to engage a surrogate strategy?
Group Leader, Antibody Lead Discovery
Bayer
Fionnuala received her PhD (Microbiology) from Trinity College Dublin in 2002. Her post-doctoral studies were carried out at Wyeth Pharmaceuticals (NY) where she worked on S. aureus antibiotic resistance mechanisms. She then transferred to the Global Biologics organization at Wyeth (Cambridge, MA; acquired by Pfizer in 2009) where she spent 5 years as a Senior Scientist working primarily with phage display in the antibody lead discovery department. In 2010, she moved to Heidelberg Germany in a role as Head of Antibody Lead Discovery for Affimed, generating bispecific NK and T-cell engagers. Since 2013, Fionnuala has been a Group Leader in the Antibody Lead Discovery department within Biologics Research at Bayer (Cologne, Germany).
Antibody Optimisation
- Are framework mutations and sequence liabilities an issue for antibody discovery?
- With an increased use of transgenic animals, the likelihood of obtaining an antibody with sequence liabilities is high. Is it worth it? Or best to go for de novo libraries with liabilities engineered out.
- What % of antibodies with sequence liabilities really do have those issues in development? Or storage?
Group Leader
Discovery Technology
Agenus Bio
Zahra Jawad received her doctoral training at the University of Cambridge in protein evolution and protein engineering. She developed phage display of zinc fingers in the chemistry department of the University of Cambridge, before moving to Domantis and phage display of domain antibodies. Zahra spent 8 years at Domantis/GSK working on therapeutic antibody programmes and bispecificis before moving onto MRC-Technology where she led efforts to generate new antibody libraries and building the antibody phage display platform. At Agenus, Zahra leads the Discovery Technology group, which focusses on bringing in new technology and platforms into Agenus and validating them.
- Mechanism of action (MOA) drives affinity decisions – how do you determine this? What if MOA is not clear?
- Select appropriate epitope then affinity-mature to gain maximal efficacy? How/when is epitope selected?
- How do you balance affinity v avidity? What assays do you do to inform this decision?
Chief Scientific Officer
Carterra
Prior to joining Carterra as CSO in 2016, Yasmina Abdiche worked for twelve years at Pfizer-Rinat where she was a Research Fellow leading a bioanalytical team discovering therapeutic antibodies and served on Rinat’s leadership team and the governing committee for Pfizer’s Postdoctoral Program. She graduated from Oxford University with a PhD in Biological Chemistry and a Master’s degree in Chemistry, and did postdoctoral research at the University of Utah. Yasmina is co-inventor of fremanezumab, an anti-CGRP antibody set for US market approval in 2018 for chronic migraine and PF-06801591, a PD-1 inhibitor currently in PhI clinical trials for cancer immunotherapy.
1:00pm – 1:30pm
- The idea that antibodies are exquisitely specific for target is no longer a given
- In vitro display-based engineering can confer off-target reactivities
- What counter screening should we be using to detect this phenotype early?
- The first report of clinical non-specificity raises a couple of important questions:
- Are we doing enough to detect off-target binding?
- Should we also be concerned for in vivo-derived antibodies?
Senior Director, BioMedicine Design
Pfizer
Orla 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.
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.
- What do we want to optimize (affinity, stability, immunogenicity, CMC, …) and how can NGS help?
- What impact does NGS have on different optimization strategies (rational design, directed evolution)?
- Can we reduce the need of optimization by designing better libraries?
Senior Scientist
ETH Zurich
Sebastian Schätzle is a senior scientist in Sai Reddy’s Lab for Systems and Synthetic Immunology in the Department of Biosystems Science & Engineering at ETH Zürich. His research focuses on antibody discovery and the analysis of immune receptor repertoires. Sebastian holds a diploma (2008) and PhD in Biochemistry (2012, Bornscheuer lab) from Greifswald University and did post-doctoral research at the University of Texas at Austin (2012-2017, Georgiou lab).
5:15pm – 5:45pm
5:45pm
Alternative Formats
Opening Address & Keynote:
- The earliest enabling technologies for multi specific antibodies are going off patent
- Will this lead to mass adoption of those methods, or will people continue to chase patentable inventive step?
- If antibody format engineering becomes commoditised, will it then squeeze out non-antibody formats?
- If not, why not?
Chief Executive Officer
UltraHuman
Jonny Finlay is the CEO of UltraHuman, an antibody drug discovery biotech in the UK that is developing a series of therapeutics for inflammation and oncology. Prior to co-founding UltraHuman, Jonny led research teams in Biologics Discovery at Pfizer and Wyeth, and carried out postdoctoral research in recombinant protein engineering at several institutes, including the Centre for Biologics Evaluation and Research, FDA.
10:50am – 11:50am
- What is the different between affinity and avidity? Why this is relevant?
- How to select highly specific nanobodies with low affinities.
- Using nanobody adaptors to regulate the “apparent affinity” of any recombinant binder
Chief Executive Officer
NanoTag Biotechnologies
Felipe Opazo studied Biotechnology Engineering at the University of Chile (Chile), he received his doctoral training at the International Max Plank School and the University of Göttingen (Germany) in neurophysiology and advanced imaging techniques. He pioneered the use of small affinity reagents in super-resolution microscopy. Felipe started his own university group developing nanobodies for accurate and quantitative imaging of neuronal synapses and immune cells. In parallel to his academic career, Felipe founded and leads (CEO) NanoTag Biotechnologies GmbH, a young start-up company that develops its own nanobody-based technologies and provides its platform services for novel nanobody discovery
- What is the optimal size for a small-format drug conjugate?
- What is the balance between PK and dosing schedule ?
- Are there targets that small formats can address that IgG cannot ?
- Can small formats overcome the current poor sentiment associated with ADCs?
Chief Executive & Science Officer,
Antikor Biopharma
Mahendra Deonarain studied at Imperial College and Cambridge University where he carried out PhD research into protein engineering. From 1997-2011 Dr Deonarain was a Principle Investigator and Reader in Antibody Technology at Imperial College, which led to some novel technologies being developed commercially. Mahendra now retains honorary links with Imperial College. He has published over 70 papers and patents in protein/antibody engineering/conjugates. In 2001, he co-founded PhotoBiotics to develop a form of targeted photodynamic therapy using antibody fragments optimized for bio-conjugation (OptiLink technology). This is now at Antikor Biopharma where he is CEO/CSO leading a team to develop the next-generation of antibody-fragment based ADCs for solid tumours based on OptiLink.
- Multispecific requirements to target solid tumors by T cells
- How to balance affinities between target and effector arm in T cell-engager molecules
- Possible combinations of T cell modulatory targets
Head Engineered Protein Therapeutics
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.
5:15pm – 5:45pm
5:45pm
Canape/Drinks Reception
Targeted Immunotherapies
- Which format for improved efficacy of TCEs?
- How to tackle solid tumors with TCEs and circumvent immunosuppressive micro environment?
- What are the current and future challenges for ACTs?
- ACTs in solid tumor indications?
- How to combine T cell-redirected therapies with other therapeutic modalities?
Director, External Research & Innovation, Immuno-Oncology
Servier
Thierry Wurch completed a Ph.D in Molecular and Cellular Biology at the University Louis Pasteur (Strasbourg, FR, 1992), followed by a post-doctoral training at the University of Ghent (BE). Back to France in 1994, he raised a molecular biology laboratory at the Pierre FABRE Research Center in Castres (FR). In 2003, he moved to the Centre d’Immunologie Pierre FABRE where he established a Molecular and Cellular Biology Department dedicated to molecular pharmacology and protein and antibody engineering. Since September 2011, he leads the immunotherapy discovery research programs at the Institut de Recherches SERVIER, the largest independent French Parma group. Since December 2016, Thierry is leading the External Research and Innovation for the Center of Therapeutic Innovation in Oncology at SERVIER.
He is currently member of the Editorial board of mAbs (Landes Bioscience) and Distinguished Advisor of The Antibody Society. He is co-author of more than 90 publications.
- Unwanted immunogenicity, still a major hurdle during drug development
- Early immunogenicity assessment: benefits and facts
- Functional screening of I/O leads to accelerate drug design
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.
12:30pm – 1:30pm
- What are the rationales for bispecific antibodies vs combination of two monoclonal antibodies?
- What are the advantages and disadvantages of tumor targeted vs systemic activation of the Immune system?
- What are the challenges of bispecific antibody based immune-activators?
Director, Immuno-Oncology
Pieris
Prior to joining Pieris Pharmaceuticals as Director Immuno-Oncology overseeing pre-clinical development of Pieris´s innovative pipeline projects, Markus Zettl was Project Leader at Boehringer-Ingelheim from 2011, leading antibody programs in the field of Immuno-Oncology from early preclinical into clinical phases.
During his PhD and postdoctoral studies, Markus worked in a variety of areas of cancer biology at the EMBL in Heidelberg Germany and at the MRC-LMB in Cambridge UK. Research topics covered molecular mechanisms of how oncolytic viruses exploit the host cytoskeleton and the impact of metallo-protease (TACE) activation on cytokine and growth factor signalling with implications for cancer and inflammatory disorders. Markus has authored numerous high impact publications and patents in the field of Immuno-Oncology.
- Why is it important to understand antibody:FcgRs interactions in immune checkpoint blockade?
- What are optimal antibody characteristics for different types of targets relevant to cancer immunotherapy?
- How is this governed by targeted receptor’s function and cellular distribution?
- Preferred human antibody isotype for novel targets and mAb: What preclinical animal models exist?
Chief Scientific Officer
BioInvent
Björn Frendéus is the CSO of BioInvent, a Swedish biotech company developingtherapeutic antibodies for treatment of cancer. Björn got his PhD studying innate immune responses to microbial infection. Over the past decades he has developed a strong interest in understanding the complex biology of antibodies in relation to their targets, and applying his knowledge to develop better antibody-based medicines. Björn’s team conceived and developed the F.I.R.S.T™ platform from which BioInvent’s lead clinical program FcgRIIB (BI-1206) has emerged, and around which BioInvent recently partnered with Pfizer to develop immunomodulatory antibodies against tumor-associated myeloid cells to boost activity and help overcome resistance to currently available checkpoint inhibitors. Several of BioInvent´s programs, including FcgRIIB and Treg, are being co-developed with the Cancer Sciences Division in Southampton, UK, where Björn is a visiting professor. Björn chairs the Swedish Foundation for Strategic Research (SSF)’s expert review committee on Infection Biology.
5:15pm – 5:45pm
5:45pm
Canape/Drinks Reception
Cell Line Development
- Cell line development is one of the critical enablers of “fast to human” clinical requirement imperative
- What are the key acceleration-enabling components of manufacturing cell line platforms
- Internal development vs. outsourcing
- Going non-monoclonal: Can the challenge create the opportunities?
- Calculated risks and how to mitigate them
Head Cell Line Development
Novartis
Zorica Dragic leads the Cell Line Development team in Novartis Biologics Center, responsible for the technical development of all manufacturing cell lines for monoclonal antibodies and therapeutic proteins from early development up to and including commercial stage.
With 12 years of experience in the Pharmaceutical industry, Zorica assumed different roles in biotechnology area. She led line function teams with the core expertise in the cell, process, and new technology development, but also led cross functional CMC teams as technical project lead, looking into technical and strategic aspects of early project pipeline. In her current role Zorica is leading team of motivated scientist at the interphase of discovery and development, assuring success of one of the fastest biologics pipelines in the industry.
- High specific productivity versus high viable cell densities
- Do high producing cell lines have high demands (for feed and oxygen)?
- Medium/Feed screen for selection of optimal combination
Chief Scientific Officer
Bioceros
Louis Boon received his Ph.D. in Biochemistry at the University of Amsterdam. In 2003 he was one of the founders of Bioceros BV were he currently hold a position of CSO. In addition, he held position as CSO for 4AZA Bioscience NV, FF Pharma and VP Preclinical for PanGenetics BV and Tanox. Louis is author of over 280 papers in international scientific journals in the field of medical biotechnology.
Since the acquisition of Bioceros by EPIRUS in 2015, Louis extended this expertise and developed a complete process modulation toolbox to fit biosimilar CQAs. After the acquisition of Epirus NL by the Polpharma Biologics group in June 2016, he has continued to work on biosimilar development and has developed the novel SPOT™ and SLIM™ upstream process technologies and continues to discover innovative new molecular antibody entities, which now within the Polpharma Biologics group can be progressed to GMP production and clinical testing.
1-2-1 Meetings / Networking Break
4:15pm – 5:15pm
- What are the most efficient approaches and techniques to demonstrate single cell origin?
- What is the current position of Health Authorities on approaches and techniques to demonstrate single cell origin?
- Is there a way the secure and accelerate the demonstration of single cell origin to reduce time to clinic?
Director, Biologics Development
Ferring Pharmaceuticals
Henri Kornmann is currently the Director of Biologics Development at Ferring, Switzerland. Prior to this role, he worked with Biogen, Medtronic and Merck on various positions in CMC Development or Manufacturing Operation. He has more than 15 year experience in Biotechnology and Medical Device Industries. Henri has a Chemical Engineering background. He holds a PhD in Bioprocess Science from the Swiss Federal Institute of technology, Lausanne.
5:45pm
Canape/Drinks Reception