Antibody Engineering & Therapeutics Europe 2024 was held in London, UK on 4-6 June, 2024. As Europe's leading antibody conference for accelerating next-generation antibodies to commercial success, topics discussed included:
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Emerging modalities: ADCs, degraders, and beyond
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Fc engineering and Fc receptor function
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Computational approaches
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Novel methods for antibody discovery
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Multispecific antibodies, agonists, conditionally active biotherapeutics
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Antibody theranostics
→ Biointron’s Highlighted Points:
1. Emerging modalities: ADCs, degraders, and beyond
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Novel disulfide rebridging and click-chemistry-based method for the generation of Fc-containing, IgG-like mono- and bispecific synthetic antibodies (SynAbs). Adaptation of this platform also made a trispecific checkpoint inhibitory T cell engager (CiTE).
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Improved target-product profile and benefit-risk profile via improvements to site-specific conjugation of payload to antibody for ADCs and bispecific extracellular degraders.
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Prioritizing medicinal chemistry for innovative linker payload design and matching disease biology with ADC design towards the development of AZ’0133 a TOP1i linker-payload.
2. Fc engineering and Fc receptor function
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Activating NK cell receptors can trigger bispecific antibodies or Fc-engineered antibodies to enhance anti-tumor NK cell responses and increase therapeutic potential of NK cell-engaging agents.
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Asparagine-linked (N-)glycosylation of Fc γ Receptor IIIa is a key regulator of antibody-binding affinity and NK cell activity. N-glycan modification and mutagenesis affects affinity and potency of NK cell responses.
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Engineered IgA can activate neutrophils against cancer, and further enhanced by interfering with the CD47/SIRPa checkpoint.
3. Computational approaches
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AbDiffuser is an equivariant and physics-informed diffusion model for the joint generation of antibody 3D structures and sequences.
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To improve collection of datasets for machine learning guided antibody engineering, we can use meta learning for noisy, under labeled, or out of distribution data or transfer learning to probe viral evolution and antibody escape.
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The second-generation Therapeutic Antibody Profiler (TAP) for computational developability triaging and rational design involves in silico developability risk prediction and can guide molecular derisking or library design.
4. Novel methods for antibody discovery
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Advanced mass spectrometry (MS) approaches like LC-MS clonal fingerprinting provide a snapshot of antibodies present in serological samples. MS may complement current discovery platforms with protein-level sequence discovery.
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Screening platform Cell Paint is used for antibody characterization by deploying in mono and co-culture setting to characterize antibody panels. This provides analysis of antibody effects in various cellular environments.
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Improving pH sensitivity of existing antibodies and selecting antibody leads with differential pH binding.
5. Multispecific antibodies
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Vγ9Vδ2 T cells are potent cytotoxic effector cells that have a natural trophism for tumors. Bispecific antibodies that recruit and activate these cells have potential with a CD123 targeting engager in preclinical development.
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IL-18R agonist bispecific antibody with activity biased towards an anti-tumor response induces IFNγ while sparing myeloid cells, which can be a tolerability issue.
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ISB 1442 is a bispecific biparatopic anti-CD38xCD47 innate cell modulator for the treatment of relapsed/refractory multiple myeloma in clinical trials.
6. Antibody theranostics
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Shortwave infrared imaging enables high-contrast targeted fluorescence-guided surgery in neuroblastoma by combining the specificity of anti-GD2 antibodies and the advantages of SWIR over conventional near-infrared imaging.
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Non-invasive molecular imaging with 18F-BMS986192 could allow characterization of brain metastases in metastatic melanoma patients to predict response.
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89Zr-girentuximab for PET/CT imaging of clear cell renal carcinoma is a highly accurate, non-invasive, well-tolerated imaging modality with promising clinical utility and practice-changing implications.
Thank you to everyone who visited our booth at BIO 2024 to learn about our services! We had a fantastic time chatting with you and how it can help you achieve antibody development. Our expert team would be happy to answer any follow-up questions. Feel free to email us at info@biointron.com or visit our website at www.biointron.com.
