PEGS Europe 2025 conference was held in Lisbon, Portugal, from November 11 to November 13, 2025. The Protein and Antibody Engineering Summit had focused sessions on bispecifics, multispecifics, machine learning, and novel target engagement strategies. The conference featured extensive technical insights into T-cell engagers (TCEs), Fc engineering, half-life extension, immunogenicity risk management, and next-generation antibody therapeutics for oncology, autoimmunity, and CNS disorders.
Trispecific TCR design with generative AI: ETC-101 was presented as a trispecific T cell engager targeting PRAME, leveraging generative models to achieve picomolar affinity and high selectivity, with no observed off-target activity.
Conditional TCEs with on/off selectivity: VHH-based TCEs demonstrated functional selectivity using avidity-driven mechanisms and high-throughput machine learning platforms to avoid off-tumor effects.
Modular recombination platform for multispecific assembly: Rapidly generating combinatorial multispecific panels uses modular antibody fragments, enabling accelerated screening and developability assessment.
FcRn-guided PK engineering: FcRn biology in IgG and albumin transport - informing half-life tuning strategies for tailored biodistribution and PK profiles in antibody formats.
Programmable Fc functional profiles via ML: ETH Zurich presented a generative ML platform that predicts Fc activity from sequence data, enabling design of antibodies with specific effector functions and reduced immunogenicity risk.
Albumin fusion formats for brain delivery: Roche shared advances in brain-shuttle antibodies cloaking ASOs, improving pharmacokinetics and blood-brain barrier transcytosis.
Afucosylated Antibody Expression →
Phage and yeast venom libraries with ML folding prediction: Peptide libraries integrated machine learning-driven foldability prediction for rapid hit-to-lead workflows using venom peptide scaffolds.
Cryo-EM + AI integration in antibody optimization: AstraZeneca and Sanofi showcased pipelines combining structural Cryo-EM data with AI-driven design for epitope targeting and lead refinement.
High-diversity VHH discovery: Platforms for small-format antibody optimization with in vitro affinity maturation and sequencing integration.
Antibody Developability Assessment →
Anti-IgA clearance for autoimmune targeting: Argenx developed anti-IgA antibodies engineered to clear circulating IgA and block FcαRI interactions, supporting therapeutic use in diseases with IgA-driven pathology.
FcγRI blocking antibodies for immune complex-mediated disease: University Medical Center Utrecht presented first-in-class Fab-optimized antibodies selectively blocking FcγRI to prevent IC-mediated inflammation in ITP and RA models.
IgG-cleaving enzyme HNSA-5487: Hansa Biopharma reported a second-generation IgG-degrading enzyme with reduced immunogenicity, designed using in silico optimization to enable clinical evaluation across autoimmune indications.
CD28xPSMA bispecifics for “cold” tumors: Regeneron discussed early clinical success of CD28 costimulatory bispecifics in prostate cancer, where combination with PD-1 blockade reactivates immune responses in non-inflamed tumors.
Bispecific HER3 antibodies: Updated preclinical and translational findings on HER3 bispecifics, aimed at tumors with poor response to HER-family–targeted monoclonals.
Bispecifics for viral peptide-HLA targeting: Immunocore presented soluble bispecific TCRs engineered to target HLA-presented viral epitopes with CD3 engagement for virus-infected cell killing.
Bispecific Antibody Expression →
Predicting nonspecificity risks: Novo Nordisk applied AI models integrating structural and sequence data to anticipate nonspecific interactions and filter candidates with better developability profiles.
Antibody generalization: Domain generalization principles to evaluate antibody-antigen interaction stability across varied design contexts.
Data-augmented design & validation: Assays enables rapid kinetic profiling (kon/koff/KD) of antibodies without purification, accelerating ML-guided binder screening in 24 hours.
Preclinical immunogenicity assessments: Workflows integrating MAPPs, T cell assays, and cytokine release testing to evaluate T-cell epitope risk in novel antibody constructs.
Optimizing expression and manufacturability: Multiple sessions emphasized modular expression systems, high-throughput manufacturability profiling, and construct-specific process development for multispecifics.
Pre-targeted radioimmunotherapy (PRIT): A half-antibody–based PRIT strategy that reconstitutes at tumor sites for reduced systemic exposure and enhanced safety.
DARPin radiotherapeutics: Optimized DARPin surface properties and albumin binders to reduce kidney accumulation in alpha-emitting radiotherapeutics targeting solid tumors.
IgE- and IgG-targeted degraders: Engineered proteases with selective IgE degradation capacity, designed using ML-enhanced platforms to reduce off-target effects and immunogenicity.
Thank you to everyone who visited our booth at PEGS Europe 2025 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.
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