Summary: The Fc domain plays a critical role in modulating the efficacy, safety, and pharmacology of antibody-based therapeutics and vaccines. Yet, most development pipelines assess only a narrow subset of Fc-mediated effector functions, risking missed opportunities and avoidable liabilities. In this presentation, Dr. Shashi Jatiani highlights how SeromYx’s high-throughput, physiologically relevant Fc profiling platform enables comprehensive evaluation of antibody function early in development. Featuring case studies across mAbs, Fc-engineered variants - including clinical-stage and marketed antibodies, and other formats, the talk illustrates how expanded Fc profiling can inform lead selection, support mechanism-of-action studies, and derisk engineering strategies with clinical relevance. Key Highlights: Comprehensive Fc Profiling Enables Functional Characterization Beyond ADCC/ADCP: Expanded assessment of effector functions such as ADNP, ADEP, and complement activation uncovers mechanistic insights missed by conventional approaches. Fc Engineering and Conjugation Strategies Require Functional Validation: Case studies demonstrate how antigen-specific FcγR binding and functional assays reveal unintended impacts of Fc silencing, half-life extension, and CAR-T conjugation methods. Fab-Fc Interplay Influences Functional Potency: Data from large antibody libraries show that Fc function varies substantially across mAbs with identical Fc domains, emphasizing the need to assess effector activity alongside Fab affinity in lead optimization.

Summary: Protective immunity depends not just on antibody titers, but also on Fc effector functions that engage the immune system through phagocytosis, cytotoxicity, and complement activation. Fc-mediated functions play a critical role in differentiating antibody quality, helping explain protection in the absence of high titers or neutralization. Comprehensive profiling across diverse immune cell types provides a more accurate understanding of efficacy and safety for both vaccine candidates and therapeutic antibodies. SeromYx’s high-throughput, antigen-specific assays and computational analytics offer powerful tools to identify correlates of protection and guide candidate selection.

Summary: As nearly all therapeutic antibodies move into the clinic with functional Fc domains, and over 45% of them Fc-engineered, developers can no longer afford to overlook the complexity and clinical impact of Fc-mediated effector functions. This comprehensive workshop from NextGen Biomed 2025, led by Dr. Silvia Crescioli, Dr. Shashi Jatiani, and Dr. Ian Wilkinson ( GammaProteins ), walks through the nuanced interplay between Fab and Fc regions, the unpredictable consequences of Fc engineering, and why early, broad functional screening is critical for therapeutic success. Highlights include: Why silencing Fc function isn’t always truly silent How tripartite Fc-FcR-antigen interactions can dramatically affect safety and efficacy Case studies revealing overlooked effector functions, like ADNP and ADEP, in anti-CD20 mAbs How SeromYx’s GCLP-certified platform enables antigen-specific Fc profiling at scale to support IND/BLA submissions

Summary: Antibody therapeutics are increasingly engineered with Fc modifications to fine-tune efficacy, extend half-life, or reduce effector function, but these changes come with risk. The complexity of Fc biology, combined with the interplay between Fab and Fc domains, means that intended outcomes don't always align with reality. In this scientific briefing, Dr. Shashi Jatiani presents real-world examples where Fc engineering led to unexpected functional changes, despite rational design, and highlights how SeromYx’s high-throughput, antigen-specific Fc effector function platform can be used to detect, predict, and optimize antibody function across development stages. Key takeaways include: Why Fc function is more than receptor binding, it’s tripartite and context-dependent Data showing how half-life extension mutations can reduce ADCC, ADNP, and NK cell activation Novel functional profiling of anti-CD20 mAbs, revealing effector functions beyond ADCC and CDC How SeromYx’s platform enables robust, scalable Fc characterization to support IND and BLA filings

Summary: Anti-CD20 monoclonal antibodies are mainstays in the treatment of B-cell malignancies and autoimmune diseases, but how well do we understand the full spectrum of their immune mechanisms? In this poster presented at Festival of Biologics 2024, SeromYx Systems leverages its high-throughput Fc effector function platform to comprehensively profile the functional landscape of rituximab, ofatumumab, and obinutuzumab. Using a full-length recombinant CD20 VLP from ACROBiosystems, the study confirms known mechanisms like ADCC, ADCP, and CDC, while also uncovering previously unreported effector functions such as eosinophil and neutrophil phagocytosis. Key insights: Biophysical FcγR and C1q binding strongly predicts functional outcomes Clear differentiation in Fc profiles across clinically approved anti-CD20 mAbs Novel functional findings may inform next-gen antibody engineering strategies