Main Conference Day 1 - CET/CEST (Cent Europe Summer, GMT+2)
Main Conference Day 1 - CET/CEST (Cent Europe Summer, GMT+2)
ADCs are hard to work with: there’s never enough sample for all your tests and they tend to aggregate before your finish testing. At Unchained Labs, we’re all about solutions that combine several measurements into one experiment, yield data fast and get you all that info from only a few microliters of sample. Join my talk to see how to use them to characterize ADC concentration, labelling, stability, and viscosity.
- Nelis Denys - Product Manager, Unchained Labs
- Kerry Chester, PhD - Professor of Molecular Medicine, UCL Cancer Institute
Analysis of the sequences of 819 antibodies and Fc fusion proteins in clinical trials reveals 55 different molecular formats and 80 Fc variants designed to modify effector function. We have now synthesized matched sets of antibodies to compare these variants directly. This presentation focuses particularly on approaches to reduce binding to Fc gamma receptors and so prevent unwanted inflammatory responses.
- Geoff Hale, PhD - CEO, mAbsolve
IgG3 is unique among the IgG subclasses due to its extended hinge, allotypic diversity and enhanced effector functions. It is also underrepresented as an immunotherapeutic candidate, partly due to a lack of structural information. Thom Sharp will present structural data of IgG3-mediated complement activation, which reveals an unexpected role of the extended hinge in pathogen neutralization, complement initiation, and C4b deposition.
- Thom Sharp, PhD - Associate Professor, Leiden University Medical Center
Due to antibiotic resistance, there is now great interest in the development of antibody-based therapies against bacterial infections, for instance via antibodies that boost the host immune system. This talk aims to provide insights into the reactivity of antibodies in a functional immune response. I will demonstrate mechanisms of antibody-dependent complement activation and phagocytosis on bacteria and highlight how important pathogens evolved mechanisms to evade antibody-mediated killing.
- Suzan Rooijakkers, PhD - Professor, UMC Utrecht
T Cell Bispecific antibodies (TCBs) are transforming the treatment of human tumors. Whereas the role and the recruitment of T cells to tumor sites following TCB treatment has been broadly documented, the role of the other immune cells remains elusive. In this presentation, we will describe the tumor microenvironment (TME) reprogramming induced by TCB treatment and elaborate on the role that the other immune cells have in modulating the response or resistance to TCB therapy.
- Marina Bacac, PhD - Head of Cancer Immunotherapy Department, Roche pRED
Human cell microarray screening enables the discovery of potential off-targets for a variety of biologics, including peptides, antibodies, scFvs, proteins, CAR T and other cell therapies. This presentation describes the generation of extensive screening libraries of expressed biosynthetic human plasma membrane and tethered secreted proteins, highlighting the role of the technology in providing specificity screening case studies relevant to safety assessment and IND submissions.
- Diogo Rodrigues Ferreirinha - European Senior Account Manager, Charles River Laboratories
Twist Biopharma, a division of twist Bioscience, combines HT DNA synthesis technology with expertise in antibody engineering to provide end-to-end antibody discovery solutions — from gene synthesis to antibody optimization. The result is a make-test cycle that yields better antibodies against challenging targets from immunization, libraries, and machine learning. Twist Biopharma will continue to optimize and expand its discovery, library synthesis and screening capabilities in partnership with others to further utilize their make-test cycle.
- Radha Parmar - Science and Technology Consultant, Twist BioScience
- Nestor Vasquez Bernat - Application Science Team Lead, Enpicom
- Christel Iffland, Ph.D. - Senior Vice President, Antibody Technologies, OmniAb
- Jason Lehmann, PhD - Senior Product Marketing Manager, Telesis Bio
- Jorge Dias, PhD - Principal Scientist, Alchemab Therapeutics
- Benjamí Oller-Salvia, PhD - Assistant Professor at IQS Barcelona, IQS Barcelona - Universitat Ramon Llull
A remaining challenge of anti-tumor antibody therapeutics is the on-target off-tumor toxicity induced by binding to target antigens expressed in normal tissues. To overcome this, we established a novel antibody technology, called Switch-IgTM, which enables antibody binding to antigen selectively at tumor sites but not at normal tissues. In this presentation, we will describe how we generated these conditionally active antibodies and their therapeutic application.
- Taishi Nishimura, PhD - Researcher, Chugai Pharmaceutical Co., Ltd.
XPAT proteins are conditionally active T cell engagers (TCEs) designed to exploit the dysregulated protease activity in tumors. In preclinical studies across multiple tumor targets, XPAT proteins demonstrated 1) Strong masking of in vitro cytotoxicity by up to 4 logs; 2) Potent in vivo efficacy at doses similar to the efficacious doses of unmasked TCE controls; and 3) Masking increases tolerated Cmax in NHP by greater than 400-fold for HER2-XPAT. A clinical trial investigating a HER2-targeted XPAT protein has been initiated.
- Volker Schellenberger, Ph.D. - Co-Founder, President and CTO, Amunix Pharmaceuticals
Several strategies have been reported to develop activatable antibodies, but most of these require sophisticated (chemo)genetic antibody engineering. Our group developed bivalent peptide-DNA locks that allow non-covalent control of antibody activity by protease activity, light or pH. In addition, I’ll present our recent development of a pH-switchable antibody-blocking protein that can be used as a generally applicable mask to allow pH-sensitive control of antibody activity.
- Maarten Merkx, PhD - Professor, Department of Biomedical Engineering, Eindhoven University of Technology
- Rene Hoet, PhD - Chief Innovations Officer, FairJourney Biologics
- Christopher Plummer, PhD - Team Leader In vitro Antibody Discovery, GSK
Developing VHH for clinical use involves many engineering steps after camelid immunization. These include humanization, affinity maturation, removal of liabilities, and engineering Protein A binding. Improving one characteristic often impairs another. We designed and built a VHH library based on the Generation 3 concept that enables bypassing many of these processes: human HCDR1-2 purged of sequence liabilities are inserted into clinical VHH scaffolds and filtered for Protein A binding. When combined with >1e8 human HCDR3s, the resultant library is able to yield VHH with drug-like characteristics.
- Andrew Bradbury, MD, PhD - Chief Scientific Officer, Specifica
Clinical drug candidates must not only have appropriate binding characteristics, but also require optimal biophysical properties. Using nuclease-directed integration we have constructed mammalian display libraries where each cell contains a single antibody gene, permitting IgG display and selection by FACS. This system is uniquely sensitive to key biophysical characteristics such as self-association and poly-specificity, enabling detection and avoidance of problematic antibodies during the initial discovery phase.
- Peter Slavny, PhD - Chief Technology Officer, Iontas Ltd.
We have generated a series of conditionally masked therapeutic antibodies that are proteolytically activated in the tumor microenvironment. Beyond masking of the antigen binding site, we also established a generic strategy of modulating effector functions of IgG1 therapeutic antibodies via Fc masking, resulting in an efficient blocking of Fc-gamma receptor binding and ADCC.
- Harald Kolmar, PhD - Professor and Head of Applied Biochemistry, TU Darmstadt
Antibody-cytokine fusions, specific to tumor-associated antigens, promise to increase the therapeutic index of the cytokine payload, as a result of a preferential localization at the tumor site. Novel strategies enable to achieve an even greater selectivity, using antibody-cytokine fusions, fulfilling the dream of “activity-on-demand” and helping spare normal tissues from undesired toxicity.
- Dario Neri, PhD - CEO and CSO, Philogen
Conditional activation enables generating more efficient antibodies by minimizing on-target off-site dose-limiting effects. By reversibly masking the antibody, binding at the target site can be maximized, thereby decreasing the effective dose and minimizing potential harm in the healthy tissue. In this talk, I will present an overview of the recent progress in the field, showing the diversity of masking strategies available and highlighting the most novel and efficient approaches. In addition, we will introduce our versatile chemogenetic antibody masking method that enables activation by proteases and other stimuli.
- Cristina Díaz-Perlas, PhD - MSCA Postdoctoral Fellow, Ramon Llull University
Mammalian display libraries can be interrogated consecutively for manufacturability and specificity. Similarly, libraries secreting antibodies are a perfect match for microfluidics-assisted high throughput screening for cellular binding or desired function, exemplifying the versatility and powerful options when combining these emerging technologies.
- Achim Doerner - Principal Scientist, Protein Engineering and Antibody Technologies, Merck Healthcare KGaA
- Erwin De Genst, Ph.D. - Senior Research Scientist, AstraZeneca
Cardiac fibrosis is a pathology typically associated with limited cardiac function, with no effective therapies currently available. Here, cardiac fibroblasts were profiled by omics technologies for target prioritization. Whole cell panning strategies using phage display technology were also explored, aiming at isolation of potential therapeutically-relevant antibodies.
- Daniel Simao, PhD - Head of Bayer Satellite Laboratory, iBET