DDW’s Megan Thomas attended PEGS Europe 2023 in Lisbon, Portugal, from Tuesday 14 November to Thursday 16 November 2023. Here, she shares insight from the annual biologics technology meeting.
Scientific tracks and presentations
Antibody-based cancer therapies
The first presentation attended in the antibody-based cancer therapies track, within the antibody drug conjugate (ADC) session, was called: ‘A new era of single-cell functional profiling for drug discovery’, presented by Kathrin Herbst, PhD, Director of Science & Business Development at Lightcast. Lightcast is developing a novel, programmable microfluidic platform that allows precise and highly flexible control of individual microdroplets using software-generated light patterns. The company’s goal is to accelerate functional characterisation and shortenoptimisation time in antibody discovery and t-cell workflows. In addition, live cells of interest can be rapidly dispensed for downstream assays as droplets remain individually addressable throughout.
Cell line and systems engineering
Following this, a presentation in the cell line and systems engineering track, focused on applying data science to enhance protein expression, ‘Using machine learning to predict protein expression’, was presented by Lovisa Holmberg Schiavone, PhD, Director, Discovery Biology, Discovery Sciences, R&D, AstraZeneca – though Holmberg Schiavone made note of the various contributors and collaborators in the poster which was being presented, including protein scientist in machine learning, Evgeny Tankhilevich. This presentation covered three primary drivers for a protein expression model: speed, cost and sustainability. “It has been a learning journey for us”, Holmberg Schiavone shared, and emphasised the importance of data sharing as a model of the future.
The next presentation attended in this track was the keynote presentation, which was given by Kate Smith, PhD, Head of UK Protein & Cell Sciences at GSK. GSK has developed high-throughput mammalian and E. coli expression systems and is using high-throughput expression pipelines to screen constructs for optimal expression to generate protein and cellular reagents. The presentation introduced the company’s high-throughput expression systems, its approaches to organising data and its design approaches.
Optimisation and developability
The final presentation attended on the first day of PEGS Europe 2023 was in the tack on optimisation and developability, within the immunogenicity risk assessment session, titled: ‘Accelerating antibody discovery for difficult targets through mRNA immunisation and beacon single cell technology’. It was presented by Francois Romagne, PhD, Scientific Director of MI-mAbs. The presentation engaged with how classical immunisation strategies and subsequent hybridoma generation often face strong limitations when it comes to poorly immunogenic membrane proteins with short extracellular domains – even though there is demonstrated efficiency in antibody generation. As such, Romagne shared how the obtention of large collections of antibodies with both molecular and function diversity against a difficult GPCR and ion channel will be described using innovative approaches combining RNA immunisation and single cell screening.
Emerging targets and therapeutic approaches
The first attended session in the emerging targets and therapeutic approaches track was the keynote within the session on innovative approaches to the challenges of solid tumours. It was presented by Xiaole Shirley Liu, PhD, CEO, GV20 Therapeutics, and titled: ‘AI-based target and antibody discovery from patient tumour profiles’. She presented on how GV20 uses bioinformatics and AI to decode natural B-cell responses from large cohorts of patient tumours to uncover novel targets and antibodies simultaneously, and has brought a first-in-class antibody against a novel innate checkpoint to Ph1 clinical trial in the US.
Advancing bispecifics and combination therapy to the clinic
Next was a luncheon presentation within the session on novel approaches. It was by Nicholas Field, Principal Scientist, Purification Development, Lonza, titled: ‘Tailored CMC solutions to overcome the challenges in bispecific, Fab and Fc-fusion protein development programs’. Lonza’s integrated CMC strategy and timeline was presented, as well as case studies highlighting key approaches and technologies, including: vector design & integration, cell line selection, downstream process, analytical method and formulation development. Field also covered the capabilities and strategies that enable acceleration of Fc-fusion, Fab fragment and bispecific antibodies through pre-clinical development.
This was followed by another presentation in the track, within the session on harnessing neutrophils using bispecifics. It was presented by Lei Shi, PhD, Senior Vice President, R&D, Biointron Biological, titled: ‘Accelerating early discovery through HTP and high-speed antibody production’. Shi talked about Biointron’s high-efficiency expression platform that enables two-week antibody production services, and how the company’s FC-MES affinity maturation system is able to provide non-biased antibody optimisation and affinity maturation in less than two months.
CAR T cell therapies and in vivo solutions
Thomas attended a presentation by Chad May, CSO of Serotiny, called: ‘Improving cell therapies with high-throughput CAR libraries’, in the session relating to optimising CARs. He shared how Serotiny has demonstrated the use of its high-throughput platform to build and deliver CARs that improve in vivo responses in preclinical studies.
Finally, Thomas attended a panel discussion which asked: ‘What is the next game changer in the CAR T cell field?’ Panel moderators included Ulf Grawunder from T-CURX and Astero Klampatsa from the Insitute of Cancer Research, and panellists included John Anderson from University College London, Michael Hudecek from University of Applied Sciences Wuerzburg-Schweinfurt, as well as Sebastian Kobold from Klinikum de Universität München. Despite the weighty topic and a limited time frame, they engaged in depth on the various ways the CAR T cell field will expand in the future, and where its success lies in the present.
Protein process development
In the protein purification session, Anis Larbi, Senior Manager Medical & Scientific Affairs, Beckman Coulter Life Sciences, presented on reducing the complexity of protein manufacturing and streamlining the workflow. In the presentation, he discussed how technological platforms integrated to a workflow improve reproducibility and robustness of the process, highlighting the various steps of protein manufacturing from inception of the idea to the final quality control of the end-product.
In the session focused on cell-based immunotherapies, Steven Quistad, Senior Applications Scientist, DNA Script, presented on how to rapidly assemble genes in a laboratory using automated enzymatic oligo synthesis. To demonstrate the utility of the company’s SYNTAX system in gene assembly, the 1.7 kb Influenza A hemagglutinin gene was used as a model system. Three double stranded DNA (dsDNA) blocks were generated from EDS-synthesised ssDNA oligos using the PCA approach followed by error correction and the dsDNA blocks were then assembled using a commercially available kit, transformed into BL21 competent cells and colonies were selected for Sanger Sequencing confirmation.
Reflecting on PEGS Europe 2023
Molecular Partners, a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, presented several of its programs, focusing on the multiple ways Molecular Partners has designed DARPins to activate the immune system against cancer only under certain conditions. This conditional activation is intended to focus immune attack more specifically against tumour cells and minimise damage to healthy cells, a major challenge for current oncology drugs and development efforts.
Meanwhile, OSE Immunotherapeutics, a clinical-stage biotechnology company working in immuno-oncology and immuno-inflammation, presented scientific updates featuring the latest progress on the company’s research programs in immuno-oncology, namely CLEC-1 (novel myeloid immune checkpoint), CYTOMASK, a new and innovative CIS-demasking cytokine linker technology, BiCKI-IL-7 (bifunctional therapy targeting PD-1 and IL-7), and Tedopi (T-cell epitope-based cancer vaccine).
From a product perspective, RedShiftBio had the Aurora protein analyser with them in Lisbon this year. With a small sample, Aurora fully and rapidly characterises biomolecules of interest, detecting structural changes early and more accurately than traditional spectroscopic methods. In their poster presentation, RedShiftBio made a structural comparison of the matrix metalloproteinases using microfluidic modulation spectroscopy (MMS), illustrating how characterising biomolecules with MMS can save both time and money.
Molecular Devices was also in attendance introducing the plasmid mini-prep starter bundle, which is scaling plasmid manufacturing with streamlined automation. Meanwhile, Azenta was ensuring attendees could learn more about the company’s GENEWIZ multiomics and synthesis solutions both on their booth and in a presentation by Crystal Richardson on innovative antibody discovery workflow, leveraging AI to prioritise leads.
The Halo Labs team was available to share insight into Aura, which enables the tool to enable full and accurate analysis of SVPs therapeutic end-products. Moreover, in the session on advances in analytical techniques and approaches, Paul Dyer, Field Application Scientist, Halo Labs, presented on the possibilities of total particle analysis with Aura and the pathway to USP validation and product release.
Bio-Rad was in attendance not just to provide insight on the exhibition floor on the company’s purification tools and antibody products, but also for two poster presentations, which included: ‘Development of IEX purification process for lentiviral vectors’ and ‘Chromatography purification of AAV8 using mixed-mode chromatography’.
Also contributing to the poster exhibit was Charles River Labs, with the following presentations: ‘Supporting CAR-T cell therapy development from discovery to IND-filing’, ‘Bispecific antibody discovery platform for IND enabling studies’, and ‘Antibody-drug conjugate off-target binding screen: Increasing the confidence in ADC safety during development’.
Promega had two posters from which to share insight, which included: ‘Cell-based luminescent reporter bioassays for immunotherapies targeting macrophage effector functions’, and ‘Development of bioluminescent no-wash Fc gamma receptor binding immunoassay to guide the development of antibody therapeutics’.
The Absolute Biotech team was available to discuss custom services, as well as the company’s comprehensive antibody reagent catalogue. They were also representing on the poster front, with a presentation on comparing potential bispecific formats comprising of trastuzumab and a humanised OKT3. The poster shows how the company systematically built and evaluated 17 bispecific designs, including a number of well-utilised formats, in order to find that Fc-containing formats and the placement of scFv can influence the expression dramatically, while discovering that interface stability for heterodimeric constructs is equally important.
Meet the exhibitor
Of course, an event such as this brings the opportunity to meet, greet, network, and learn from various exhibitors showcasing their work and recent milestones.
Sartorius was presenting at the event, featuring Field Application Specialist, Gail Calvert, who discussed leveraging integrated and advanced technologies for successful cell line development, the team was also at hand to outline solutions for single cell, clone and colony analysis, screening and isolation, live-cell imaging and analysis, as well as label-free biomolecular interaction analysis. Not to mention, Polypus, a French lab technology company acquired by Sartorius earlier this year, had expert Marine Houdou on hand to discuss modular DNA assembly to recombinant protein production at Polyplus, as well as poster presentations on how to improve protein production yields in mammalian cells through plasmid engineering and transfection optimisation.
Alongside a presentation by Jyotsna Venugopal, Director, Product Marketing, Telesis Bio, on automated solutions for overcoming synthesis bottlenecks in CAR-T cell therapy workflows, the experts at the company’s booth provided the opportunity for attendees to find out how Telesis Bio’s BioXp solutions heave enabled optimisation of CAR generation workflows, and the assembly of optimised CARs; generation of mRNA for T cell manipulation, enabling rapid candidate screening through transient modulation of cellular phenotypes; as well as automated overnight synthesis of lead candidates across biologics discovery workflows.
Sphere Fluidics presence on the exhibition floor was bolstered by a presentation from Richard Hammond: ‘Picodroplets for cell Line engineering: A novel automation approach’. Between these, the company was introducing the Cyto-Mine platform, which enables a step-change in speed and scale of working. In his presentation, Hammond showed how microfluidic-enabled picodroplets deliver integrated, user-friendly, automated workflows where millions of individual cells are assessed daily, and the best single cells selected – in an environment that maintains high cell viability and outgrowth.
Revvity was involved with both the event talks and the posters, as well as having a team of experts on the booth. Ana Rebocho, Manager, BioP R&D of Revvity, presented on accelerating biologic development programs with a state-of-the-art CHO expression system within the session on automation and process optimisation in the ‘Protein process development’ track. In addition, the company presented three posters: ‘Integration of next-generation transposon vectors with state-of-art host cell lines’, ‘Application of gene editing technologies to improve biotherapeutic manufacturing’, and ‘CHOSOURCE ADCC+ cell line for enhanced therapeutic potency’.
By visiting the Icosagen booth, attendees had the opportunity to hear more about the company’s clinical and preclinical competencies can translate research ideas into functional, GMP-ready proteins. Additionally, Icosagen CSO Mart Ustav Jr was presenting on how cancer cells react when deprived of glucose. Meanwhile, the Malvern Panalytical booth gave attendees the possibility to speak to company experts, as well as to see how products work – including the opportunity to play Malvern’s Kahoot game.