ON-DEMAND PRESENTATIONS

Oral delivery of antibodies directly to intestinal tissue would allow IBD treatment without systemic exposure or injections. Sorriso VHH single domain antibodies are engineered for stability among intestinal and inflammatory proteases, enabling oral dosing. SOR102 is an anti-TNF/IL-23p19 bi-specific formulated into room-temperature stable enteric-coated mini-tablets. On exposure to intestinal trypsin, the SOR102 trypsin-labile central linker is cleaved, liberating each monomer for intestinal tissue entry. SOR102 was evaluated in healthy volunteers and ulcerative colitis (UC) patients in a Phase 1 first-in-human study (NCT06080048). SOR102 was safe and well tolerated with minimal systemic exposure. However, consistent micromolar levels of active monomers were detected in UC patient feces and monomers were measured in UC colonic tissues. In the SOR102 BID arm, there was a strong alignment between UC clinical activity, tissue [drug], and pharmacodynamic outcomes. Thus, SOR102 delivered local TNFa/IL-23 inhibition within the inflamed GI tissue of UC patients, while limiting systemic exposure.

Neonatal Fc receptor is a popular target for treatment of autoimmune disorders due to its role in maintaining IgG levels. Fc-ABDEG and albumin-binding VHH were combined to develop next-generation FcRn blockers with improved IgG clearance. Step-wise engineering was applied to optimize position and number of VHHs, their affinity to albumin, and the linker connecting it to Fc-ABDEG. Novel FcRn-based cellular assays and effects in human FcRn transgenic mice are included.

Bio-Rad’s Pioneer™ Antibody Discovery Platform features a vast Fab library (>2 × 10¹¹ sequences), optimized for selection and developability. Using SpyDisplay and the TrailBlazer™ platform, it enables rapid discovery of lead candidates, including GPCR-targeting antibodies with performance comparable to clinical benchmarks. We’ll also present SpyLock, which is a novel approach for fast generation and high-throughput functional screening of bispecific antibodies.

Antibody Drug Conjugates (ADCs) are rapidly changing the clinical treatment of cancer, and these sophisticated therapeutics have multiple interactions within the tumor microenvironment (TME) that are important for drug design. In this talk, I will share our experimental and computational results highlighting the impact of the TME on the ADC, including macrophage and protease effects, and the impact of the ADC on the TME, such as immune activation.

Add-on this optional pre-conference workshop to your main conference registration package and gain a comprehensive overview of antibody engineering in an easy-to-follow classroom setting to help you prepare for the main conference program.

• Workshop registration begins at 7:30 am
• Morning Break: ~10:30-10:50

WORKSHOP OVERVIEW

Today’s wealth of knowledge of antibody structures will be reviewed along with the genetics of diversity generation, to give insights into the best strategies for improving function. There is particular emphasis on the choice of a functional assay to effectively monitor the changes in a desired property, and the use of functional enrichment steps where a library approach is employed. Not only is amino acid sequence amenable to engineering, but glycan structures and other modifications may also be engineered. The course will focus on the engineering and enhancement of antibodies and antibody-like scaffolds. Examples will include work on antibody fragment affinity improvement by 100-fold to low pM affinity. Also, the engineering of bispecific antibodies by diverse approaches and the adaptation to generate Chimeric Antibody Receptor (CAR) constructs will be discussed. Expression platforms for producing antibodies for testing and for manufacture will also be covered. A background in biochemistry and molecular biology is useful, as the course is designed to progress rapidly from simple to advanced concepts.

INSTRUCTOR
David Bramhill, Ph.D., Founder, Bramhill Biological Consulting, LLC

WORKSHOP AGENDA

• Functions amenable to engineering: affinity, specificity, stability, solubility, immunogenicity
• The measure of success: functional assays
• Engineering by design
• Engineering by random mutation
• Designed libraries
• Display technologies
• Improving manufacturing by protein engineering methods
• Glycosylation engineering – function and homogeneity
• Other protein modifications
• Immunogenicity engineering
• Bispecific antibodies
• CAR-T strategies
• Expression of antibodies and fragments for discovery and testing
• Manufacturing platforms for antibodies and fragments

NOTE: The afternoon workshop “Introduction to Bispecific & Multispecific Antibodies” is an excellent complement to the morning introduction course.

The Singularity Suite represents a new class of genetically engineered mouse models designed exclusively for single-domain antibody (sdAb) discovery. Each model features a streamlined, minimalist humoral immune system optimized to generate high-diversity, high-fidelity sdAbs with exceptional stability, solubility, and developability. The Singularity Suite encompasses an unprecedented scaffold spectrum including human VH, human Vκ, camelid VHH, shark VNAR, dog VH, cat VH, and mouse VH, enabling broad utility across therapeutic, diagnostic, and animal-health applications. Integrated with high-throughput, sequence-first workflows, these platforms enable rapid generation of potent, developable modular binders against complex targets, and are accessible through flexible licensing and service partnerships.

We will discuss the pros and cons of bispecific T-cell engagers (TCEs) relative to CAR-T cell therapies as well as protein-engineering strategies that can be employed to address limitations of TCEs for cancer therapy.

Gyes Bv is a science-driven biotech start-up committed to exploring new frontiers in antibody therapeutics. We developed the Multispecific Antibody Platform, which we use to discover and develop precision multifunctional antibodies that build on novel insights in avidity engineering. Here I will discuss our progress in designing antibodies that become conditionally active upon binding to combinations of targets co-expressed on select cell populations.

Biocytogen provides a unique, fully characterized library of fully human antibody binders targeting over 1,000 druggable proteins. Several bispecific ADC assets, utilizing a common light chain and our proprietary Top1 payload, are now in clinical trials. RenNano mice generate fully-human nanobodies for next-generation ADC.

As the field increasingly recognizes the limitations of traditional cytotoxic payloads, differentiation through novel mechanisms of action has become essential. Amanitin-based ADCs, with their unique inhibition of RNA polymerase II, exemplify this next wave of innovation, designed to overcome resistance mechanisms. The Phase I/IIa experience with HDP 101, an anti-BCMA ADC with amanitin as novel payload, provides a clear view of the translational path associated with developing a first in class ADC payload. During dose escalation and at doses below the MTD, HDP‑101 has demonstrated objective responses, including complete remissions, in patients refractory to currently available therapies, including prior treatments directed at the same target.

While IL-2 has been shown to be key cytokine for the promotion of T-cell proliferation and effector function, its clinical use for cancer immunotherapy has been limited by severe toxicities. This talk describes the pre-clinical development of REGN10597, a PD-1 targeted receptor masked wild type IL-2 that demonstrates potent in vitro and in vivo activity when targeted to PD-1 expressing T cells but lowered systemic activity in the absence of targeting.

Artificial intelligence (AI) is transforming antibody discovery and engineering. Ailux's platform synergistically combines the best of our comprehensive wet lab, AtlaX biologics database, and three proprietary AI engines. We will explore our latest case studies that exemplify our AI-driven approach for tackling challenging targets, identifying unique functional antibodies, and achieving multi-objective optimization. This presentation provides our realistic and evidence-based perspective on the impact of AI on developing next-generation antibody therapeutics.

This talk explores how Alloy is redefining T cell engager bispecific antibody discovery through integration of precision affinity design engineering and high throughput functional characterization. By systematically tuning both CD3 and target-arm interactions, we decouple efficacy from cytokine-driven toxicity, resulting in an expanded therapeutic window and enabling safer immune engagement in oncology and autoimmunity. Leveraging a comprehensive, data-rich functional screening workflow, Alloy delivers potent, first-in-class bispecifics tailor built for real-world translational impact.

We have previously demonstrated that an IgG3 agonistic TLR4/MD2 antibody reversed acute murine Type 1 Diabetes (T1D) through induced immune tolerance. To translate this work to humans we developed novel human TLR4 agonistic antibodies, demonstrated that the IgG3 isotype and enhanced multivalency are necessary for their TLR4 signaling, and demonstrated their tolerogenic potential for treating inflammatory diseases.

Current Treg-depleting strategies often affect both tumour and effector T cells, limiting therapeutic benefit. A target-agnostic cell-panning approach using the n-CoDeR phage display library identified antibodies that selectively target tumour-associated Tregs. These antibodies recognised both familiar and novel Treg targets, including a distinct ICAM-1 domain, achieving tumour-specific Treg depletion while sparing peripheral cells. This suggests potential for improved cancer immunotherapy and supports unbiased discovery of therapeutic antibodies.   

Antibody-based approaches targeting respiratory viruses such as influenza and corona have gained momentum. Traditionally, efforts have focused on systemic or subcutaneous administration. More recently, focus has shifted to intranasal administration for protection at the portal of entry. Preclinical efficacy and human safety studies have explored the challenges and advantages of local antibody delivery.

Traditional antibody discovery approaches often prioritize single objectives, failing to balance multiple properties simultaneously which yield candidates with compromised developability profiles. We present a selection framework using Pareto optimization across rank-normalized scores with hierarchical property classification. This approach generates balanced candidate shortlists with AI-assisted explanations of property trade-offs, enabling efficient identification of optimal molecules for validation while reducing costly experimental iterations and accelerating therapeutic antibody development.

AI/ML for biotherapeutics is constrained by the scale and quality of training data. In this session, Twist Bioscience will present multiple workflows for strategies to bridge this gap using high-fidelity synthetic DNA platforms and bespoke data outputs that integrates next-generation synthesis and production and characterization directly into the Design-Make-Test-Learn cycle. Case studies will illustrate how LLMs are validated using Twist “off-the-shelf” data sets, how high-throughput iterations of make-test cycles can be used to compare and train new models, and when in silico (de novo) designed libraries coupled with wet-lab panning and screening can simultaneously generate lead therapeutic candidates while also validating and training generative models. Join us to learn how scalable and innovative antibody services transform ML into a powerful engine for rapid biotherapeutic discovery.

Fibrosis can affect multiple organs in the human body and significantly threaten human health. Early diagnosis and intervention are crucial for preventing disease progression. However, very few treatments are available to patients. Next-generation medications with novel mechanisms of action are demanded to broaden the responding patient population and improve the therapeutic index. WNT1-inducible signaling pathway protein 1 (WISP1, also known as CCN4), a matricellular protein, was identified as a novel drug target for fibrosis through analysis of the transcriptomic data of human cirrhotic livers. I will present the preclinical studies of targeting WISP1 for treating tissue fibrosis.

Add-on this pre-conference training course to your main conference registration package for an additional fee and gain a comprehensive overview of antibody engineering in an easy-to-follow classroom setting to help you prepare for the main conference program.

• Training course registration begins at 8:00am.
• Break Schedule:
  • AM Break: 10:30-11:00;
  • Lunch: 12:30-1:30;
  • PM break: 3:00-3:30

TRAINING COURSE OVERVIEW

Today’s wealth of knowledge of protein structures will be reviewed along with the genetics of diversity generation of antibodies, to give insights into the best strategies for improving protein function. There is particular emphasis on the choice of a functional assay to effectively monitor the changes in a desired property, and the use of functional enrichment steps where a library approach is employed. Not only is amino acid sequence amenable to engineering, but glycan structures and other modifications may also be engineered. The course will focus on the engineering and enhancement of antibodies and antibody-like scaffolds. Examples will include work on antibody fragment affinity improvement by 100-fold to low pM affinity. Also, the engineering of bispecific antibodies by diverse approaches and the adaptation to generate Chimeric Antibody Receptor (CAR) constructs will be discussed. Expression platforms for producing antibodies for testing and for manufacture will also be covered. A background in biochemistry and molecular biology is useful, as the course is designed to progress rapidly from simple to advanced concepts.

INSTRUCTOR

David Bramhill, Ph.D., Founder, Bramhill Biological Consulting, LLC and Research Corporation Technologies

COURSE AGENDA

• Functions amenable to engineering: affinity, specificity, stability,

solubility, immunogenicity

• The measure of success: functional assays

• Engineering by design

• Engineering by random mutation

• Designed libraries

• Display technologies

• Improving manufacturing by protein engineering methods

• Glycosylation engineering – function and homogeneity

• Other protein modifications

• Immunogenicity engineering

• Bispecific antibodies

• Antibody-drug conjugates (ADCs)

• CAR-T strategies

• Expression of antibodies and fragments for discovery and testing

• Manufacturing platforms for antibodies and fragments

This session will offer perspective on what it takes to create value for biotechnology companies with a focus on early-stage (seed and Series A) therapeutics companies.

Optimizing antibodies for efficacy requires careful consideration of several factors, including biology, modality selection, ADME (adsorption, distribution, metabolism, and excretion) and developability. In this workshop, we will provide an overview of these topics and share examples to highlight their importance.

ADCs and eTPD specifically depend on efficient lysosomal trafficking for activity. Here we leveraged the well-characterized low-density lipoprotein receptor (LDLR), and engineered bispecific LDLR-targeting chimeras (LIPTACs), for efficient degradation of extracellular membrane proteins. We further developed degrader–drug conjugates that intentionally hybridize eTPD with ADCs for greater efficiency of drug payload delivery. This platform broadens the therapeutic potential of antibody-based modalities.

T cell engagers are highly potent immunotherapeutic modalities. However, their broad application is constrained by on-target, off-tumor toxicity and CRS, resulting in a narrow therapeutic index. We present the development of a conditional, dual-antigen targeting trispecific TCE (TriMab) that integrates a synapse-gated design with affinity-tuned binding arms to achieve AND-gated tumor selectivity. Our work establishes synapse-gated, dual-targeting trispecifics as a next-generation framework for engineering safer and more precise T-cell therapeutics

T cell engagers (TCEs) show promise in solid tumors but are constrained by cytokine release and on-target, off-tumor toxicity. Amberstone’s T-MATE™ platform overcomes these barriers with a pH-gated, target-selective mechanism that adapts to tumor pH heterogeneity while maintaining an optimal therapeutic profile. This conditional strategy enables a new generation of TCEs that combines both safety and efficacy with broad applicability across diverse solid tumor indications.

Our logic-gated CD3 Switch-DARPins are designed to overcome current limitations of T-cell engagers, such as the lack of clean targets and poor therapeutic windows. We developed a MSLNxEpCAM-targeted Switch-DARPin that contains CD2 costimulation and a masked CD3 moiety that is released to activate T cells only when both TAAs are co-expressed on target cells. This format allows for increased tumor specificity via rational selection of tumor target combinations.

This presentation will cover the discovery and engineering of XmAb942, a potential best in class high-affinity anti-TL1A monoclonal antibody with extended half-life, and a first-in-class bispecific antibody targeting TL1A and IL-23p19. Both candidates are designed for therapeutic use in Ulcerative Colitis and Crohn’s Disease.

TCR specificity to peptide-HLA antigens is central to immunology, impacting responses in infection, autoimmunity and cancer. Achieving precise recognition while avoiding off-target reactivity is critical for effective immunity and safe therapeutic interventions. Comprehensive, proteome-wide specificity profiling of TCRs is challenging with current methods, which notably lack integrated machine learning for large-scale analysis. Here, we report a synthetic immune cell system coupled with machine learning to enable TCR functional and specificity mapping of peptide-HLA antigens at proteome-scale.

Each antibody format introduces unique structural and functional variables that can significantly alter Fc effector activity. Assessing therapeutic antibodies on SeromYx’s high-throughput, GCLP-accredited Fc effector function platform enables empirical and format-agnostic profiling of developmental candidates. Our platform has helped uncover critical, early insights into the therapeutic activity and safety of diverse antibody formats, guiding development with data-driven decisions.

Add-on this optional pre-conference workshop to your main conference registration package and gain a comprehensive overview of bispecific and multispecific antibodies t in an easy-to-follow classroom setting to help you prepare for the main conference program.

• Workshop registration begins at 12:30 pm
• Afternoon Break: ~ 3:30-3:50

WORKSHOP OVERVIEW

This workshop covers the key aspects of bispecific antibody design, how best to achieve desired therapeutic function, and then explores the challenges posed for manufacturing such complex molecules. The various parameters for a bispecific antibody are each examined – valency and affinity for engaging each individual target, optimum physical distances for desired binding and outcome, requirement for Fc function(s) or not, etc. A discussion of antibody formats that may be especially applicable to rapid screening of the optimum valency, affinity, spacing, etc., of each specific binding component is included. It is aimed to provide even beginners with explanations of the nomenclature and science.

INSTRUCTOR
David Bramhill, Ph.D., Founder, Bramhill Biological Consulting, LLC

WORKSHOP TOPICS TO BE DISCUSSED

• Review of Antibody Structure, Fc Function(s)
• Fundamental Bispecific Antibody Design Considerations
• Symmetric vs. Asymmetric Formats – Valency of Target Binding
• Is Fc Function Required for a Particular Bi-specific Antibody Therapeutic?
• Aligning Format with Desired Bispecific Antibody Function
• Examples of a Variety of Bispecific Antibody Applications, from T-Cell Engagers to crossing the blood-brain barrier
• Manufacturing Multi-subunit Bispecific Antibody Molecules

WHAT WILL YOU LEARN?

• Gain an overview of the key aspects for design parameters for Bi-specific Antibodies.
• Scientific terms and acronyms relating to Bi-specific Antibody will be defined and explained.

We developed a novel functional screening method using hyperphage display platform that allows rapid discovery of potent antiviral single domain antibodies. We benchmarked RASP against established phage ELISA and deep sequencing methods. RASP can be used either as a standalone platform or seamlessly integrated with conventional screening methods to accelerate the discovery of antiviral VHHs.

Rigaku developed an EDT technology that can image huge molecules and complexes in solution without prior information or the need for crystallization/freezing/fixation/labeling processes. This enables overnight direct epitope mapping, molecular defect and aging monitoring during culture and purification processes, nucleotide-protein quantitation of vector complexes, and observation of defects in particles using the molecular 3D image under specified conditions.

My group engineers genetic systems that dramatically accelerate the speed of mutation and gene evolution in vivo so that we can drive the rapid evolution of new biomolecular functions and prospectively watch (and systematically manipulate) the course of long gene evolutionary processes on laboratory timescales. I will share recent developments in the use of our continuous evolution system, orthogonal DNA replication system (OrthoRep), to evolve antibodies. I will discuss our efforts to affinity mature antibodies at scale along with the intersection of computational antibody design and evolution, including work focusing on prioritizing sequence space exploration to generate data for training computational models.

Alloy’s integrated antibody discovery and optimization platform combines yeast display with cell-based screening to deliver high-affinity, biologically relevant antibodies with rapid turnaround. By uniting on-cell binding validation with
quantitative affinity maturation, Alloy expands what is druggable across low copy number and structurally complex targets. This approach enables multi-parameter antibody discovery and optimization, and has demonstrated success across challenging programs, accelerating the path from initial discovery to viable therapeutic candidates.

To address critical challenges in ADC discovery, such as elucidating mechanisms of resistance and systematically identifying synergistic payload combinations, Turbine integrates transcriptomic, genomic, and protein–protein interaction data into computational “virtual cell” models. These models are trained on perturbation-response profiles to accurately recapitulate cellular behavior. In this presentation, we highlight the application of our virtual-cell–based screening framework for prioritizing synergistic payload partners, complemented by automated in vitro validation and mechanistic simulations that enable detailed interrogation of resistance pathways.

Current extracellular targeted protein degradation (eTPD) strategies primarily rely on recycling receptors and lysosomal trafficking for internalization and degradation. Here, we developed bispecific antibodies that recruit membrane-bound proteases to proteins of interest, enabling their “degradation” them via enzymatic shedding. Additionally, the induced proteolysis releases soluble ligands that may influence downstream cellular processes. This approach provides a new mechanism of eTPD and broadens the scope of antibody-based therapeutics.

Traditional antibody discovery approaches often prioritize single objectives, failing to balance multiple properties simultaneously which yield candidates with compromised developability profiles. We present a selection framework using Pareto optimization across rank-normalized scores with hierarchical property classification. This approach generates balanced candidate shortlists with AI-assisted explanations of property trade-offs, enabling efficient identification of optimal molecules for validation while reducing costly experimental iterations and accelerating therapeutic antibody development.

Bispecific antibodies (bsAbs) can enable therapeutic mechanisms, such as dual antigen targeting or receptor agonism, that are impossible using monoclonal antibodies. BsAbs with IgG-like format (bsIgG) are comprised of two unique heavy chains, each having a cognate light chain. Co-expression of these four unique polypeptides often leads to several mispaired species that are difficult to separate from the target bsIgG due to their similar biophysical properties. Here we describe a set of mutations called ProAla that exploit a the unfolded protein response pathway of cells. ProAla heavy chains are engineered with higher folding energy barriers such that only the cognate light and heavy chains can induce folding, chaperone release and secretion. The structures of the ProAla Fab and Fc regions are identical in structure to normal antibodies, enabling maintenance of half-life and function. Mispaired polypeptides fail to secrete from the cell due to enhanced interaction with the endoplasmic reticulum chaperone BiP, resulting in increased purity of secreted bsIgGs.

In this talk, we present the CHO Edge System, which integrates a glutamine synthetase (GS)-CRISPR knockout CHO host, a hyperactive transposase, libraries of characterized genetic elements to control cellular functions, and computational tools for rational vector design and multi-omics analysis. We present case studies highlighting the impact of these tools to optimize expression for both standard monoclonal and bispecific antibodies.

Here we present the development and characterization of OmniUltra transgenic chickens, a novel platform for generating human antibody therapeutics with bovine-inspired ultralong CDRH3. This platform maintains the evolutionary distance advantage of a divergent host species, enabling robust immune responses to mammalian-conserved targets, while utilizing a novel structural format to provide unique paratopes for accessing cryptic epitopes, as well as small autonomous binding units for constructing multispecifics.

This presentation will explore how Twist Biopharma Solutions leverages data-driven antibody discovery with hyperimmune and humanized mice to maximize hit rates, accelerate timelines, and improve success against even the most challenging oncology targets

Ability Biotherapeutics presents AbiLeap™ – a proprietary AI-enabled platform to systematically generate conditionally active antibodies. Trained on one of the largest therapeutic antibody databases, AbiLeap achieves unprecedented mutational reach (up to 25 amino acid changes) while retaining epitope specificity and therapeutic-ready humanness. Using AbiLeap we have generated leads against 4 targets and are pursuing IND-enabling studies by 2027.

Successful development of a T-cell engager relies on specifically localizing cytotoxicity to tumor cells of interest with minimal off-tumor activity across the body. Cartography's ATLAS and SUMMIT platforms analyze genome-wide expression profiles to optimally select single antigens and antigen pairs whose expression are restricted to cell populations of interest. This talk will discuss how these platforms have translated into the development of CBI-1214 and other T-cell engagers in Cartography’s pipeline.

Nucleome Therapeutics tackles the molecular causes of inflammatory diseases through a breakthrough approach to 3D human genetics. NTP464 is a novel inflammation checkpoint identified using Nucleome’s proprietary suite of genetic approaches. Through understanding how genetic variation in patients living with autoimmune disease impacts the genome’s physical 3D interactions with protein-coding genes, Nucleome has uncovered a profound multi-cellular orchestrator of inflammation resolution with potential to move beyond current advanced therapeutics.

The use of T-cell engagers in solid tumors is currently limited by the availability of antigens that distinguish cancerous from healthy tissues. Using a lab-integrated, AI/ML-driven antibody engineering platform, we demonstrate that potent T-cell engagers can be rapidly generated against well-known solid-tumor targets, achieving robust tumor clearance without the typical on-target toxicities. We highlight case studies featuring both avidity-based and Boolean logic-controlled T-cell engager architectures across multiple solid malignancies.

Design and Conjugation strategies to enable transformative therapies. How the CysTyr platform enables production of novel targeted combination therapies with greater efficacy and safety

Implementing high throughput developability workflows early in biologics generation guides optimized lead selection. Addressing sequence liabilities, chemical modifications, immunogenicity, and biophysical issues accelerates development and reduces failures. Complex formats like antibody-drug conjugates and bispecifics pose challenges requiring tailored strategies for successful developability and clinical outcomes.

We leverage our discoveries which show that blockade of innate immune regulatory pathways can halt and even reverse lung fibrosis. We aim to develop novel, multivalent Ab constructs that simultaneously block the activity of these profibrotic pathways.

Cell surface proteins are key regulators of cellular signaling, metabolism, and interactions with the surrounding environment. A promising approach to modulating their function is through the control of endocytosis and intracellular trafficking. Under normal physiological conditions, cells use these processes to maintain membrane protein homeostasis and attenuate signaling, yet their therapeutic potential has only recently begun to be explored. In this talk, I will discuss how bispecific antibodies can be designed to modularly control membrane protein endocytosis and signaling, including for growth factor receptors and G protein–coupled receptors, and describe the underlying mechanisms by which these molecules function, with comparisons to traditional antagonists and their potential clinical implications. I will also share mechanistic insights into Ivonescimab, an anti-PD-1/VEGF antibody, and how its mechanism may differ from the use of anti-PD-1 and anti-VEGF antibody combination therapies.

Triaging and transitioning a large panel of prospective antibody “hits-to-leads” is de-risked when biology, developability, and manufacturability attribute assessments are integrated by design. ATUM’s services for advancing discovery sequences to a manufacturable biologic with phase appropriate assessments will be outlined. These include AI and in silico screening, high-throughput transient expression for rapid material generation and developability assessment for rank ordering hits. Selected leads are transitioned to an intermediate, higher yield system for high resolution analytics and a manufacturing predictive selection process. Finally, iterative knowledge gained is seamlessly executed in a commercial manufacturing-ready cell line.

BigHat Biosciences uses AI/ML and a high speed automated wet lab to rapidly design and optimize safer, more effective therapeutic antibodies. Our platform combines machine learning with experimental data to iteratively improve candidates based on key properties such as affinity, function, and developability. We've leveraged our platform to create antibodies with enhanced functionality, such as pH selectivity, logic gating, and avidity-optimized T cell engagement, demonstrating the power of AI/ML to overcome key challenges in antibody development.

Therapeutic peptides are an important class of drugs offering advantages over both small molecules and antibodies due to their combination of high target specificity, structural flexibility, and low immunogenicity risk. Unlike traditional peptide drug discovery that relies on rational design or natural scaffolds optimized with in vitro methods, we introduce OmniUltra, a platform to generate structured peptides to human drug targets through in vivo optimization of ultra-long HCDR3 "knob" sequences in a divergent host species. We describe the isolation of knob-derived peptides as high-affinity and highly specific autonomous binding units.

Therapeutics in inflammatory indications often are limited in their efficacy. Blockade of multiple pathways by targeting multiple cytokines with a single agent is a way to enhance efficacy and benefit to patients. We describe the engineering of trispecific antibodies with high-affinity neutralization of three cytokines simultaneously. Design factors to be discussed include domain arrangement, strategies for driving correct chain pairing, and optimization for expression, stability and developability.

Degeneration of retinal neurons in mammals leads to irreversible vision loss. We discovered that Prox1, a homeobox protein, is transferred from neurons to Müller glia (MG) to suppress regeneration. Blocking this transfer with our Anti-PROX1 therapy reactivates MG’s regenerative potential. This approach successfully delayed vision loss in disease model mice, offering a promising strategy to treat retinal degenerative conditions by restoring the intrinsic repair capacity of the mammalian retina.

In this presentation, I will describe how allometric scaling from the Tg276 humanized FcRn model enables accurate early-stage projection of antibody clearance and half-life in humans. I will outline the translational performance of the model across diverse antibody formats and show how the Tg276 model supports efficient lead selection, reduces reliance on NHP studies, and accelerates therapeutic antibody development.

Targeting pHLA class I and II at therapeutic resolution has been largely restricted to approaches building on the native TCR ligand as biologics or cell therapy. We here show how the special pIX phage display system has been optimized and combined with in silico guidance and deep sequencing as a unique platform allowing TCR-Like antibodies to enter this stage beyond the current state of the art.

OASIS is a European research program dedicated to optimizing the clinical use of antibody–drug conjugates (ADCs) by addressing resistance mechanisms. Through a multimodal approach integrating spatial tumor microenvironment profiling, genomics, liquid biopsies, and artificial intelligence–driven predictive modeling, OASIS aims to identify biomarkers of response and guide patient stratification. The project brings together academic, clinical, industrial, and patient partners to accelerate precision oncology.

Gyes is a science-driven biotech focused on advancing antibody therapeutics through the rational engineering of multispecific formats. We have developed a Multispecific Antibody Platform that leverages avidity engineering to design next-generation antibodies with enhanced selectivity and controllable functionality. Our approach enables conditional activation through the combinatorial engagement of co-expressed targets on defined cell populations. This mechanism allows selective modulation of immune cell function, improving therapeutic precision while minimizing off-target activity.

Conditional logic-gated bispecific ADCs can be optimised to enable precise tumour targeting while delivering deeper and broader efficacy by integrating dual-antigen recognition. This approach enhances potency, mitigates on-target/off-tumour toxicities, and addresses intratumoural heterogeneity. The talk will highlight engineering principles, preclinical validation, and translational insights advancing this next-generation ADC modality.

Antibodies targeting human cytomegalovirus (CMV) exhibit limited efficacy due to immune evasion mechanisms, including viral receptors that capture human Fc domains. We engineered Fc variants that retain binding to host receptors but exhibit markedly reduced binding to viral Fc receptors. Antibodies with engineered Fc domains mediated enhanced CD16A activation and limited viral spread in CMV-infected fibroblasts more effectively than wild-type Fc.

We present JAM-2, a fully computational antibody design platform that produces VHH-Fc and full-length mAbs with drug-like affinity and developability. Across 16 unseen targets and in under a month, JAM-2 achieved 100% target coverage with double-digit percent bind rates and frequent picomolar to single-digit nanomolar binders from just tens of designs tested. JAM-2 also directly generated GPCR-targeting antibodies in native cellular contexts, delivering lead-quality molecules without post-hoc optimization.

Antibodies are one of the most studied molecules to date, and they have proved to be successful biotherapeutics as well as critical reagents for both basic and applied research. The wealth of information about antibodies has afforded investigators the ability to modify critical functions of antibodies through sequence-based and/or structural modifications. One key function of antibodies is to serve as a bridge between innate and adaptive components of the immune system. This is accomplished in part through engaging target antigen through the variable regions, and then engaging humoral and cellular components of the immune system through the fragment crystallizable (Fc) region. Fundamental sequence and structural insights have afforded investigators the ability to impart novel functionalities, but at times with unintended consequences. The intent of this review is to provide a historical perspective on critical insights that have informed modern Fc engineering efforts and how these efforts have led to antibodies with enhanced or novel functionalities. Discussion will also be presented on how the emerging field of computational protein engineering could provide new opportunities to modulate antibody Fc effector functions.

TfR1 shuttles show promise for CNS therapeutics, but toxicities remain limiting. We introduce a high-throughput in vivo screening method to engineer novel brain shuttles. Powered by AI and Manifold's protein barcoding technology, our approach reveals novel shuttle targets and shuttles with enhanced tissue selectivity, reduced toxicity profiles, and optimized biodistribution.

Adeno-associated virus (AAV) gene therapies face challenges in tissue-specific delivery and safety. We have developed bispecific Altibody for precise AAV retargeting to muscle and CNS. This innovative "plug-and-play" approach enhances on-target transduction efficacy and safety in mice, marking a milestone in AAV retargeting strategies for gene therapy applications.

Recent advances in generative models for protein design have greatly accelerated the computational discovery of de novo proteins that bind biological targets of interest. These advances have vastly outpaced experimental validation, creating a bottleneck for the full realization of protein design for biological applications. I will present a massively parallel synthetic biology approach to validate thousands of designs against thousands of targets, bringing us closer to using protein design to interface with biology at the scale of proteomes.

The precise depletion of immune cells is a key therapeutic strategy for a wide variety of autoimmune diseases. Recently, T cell engagers have been used to redirect T cell cytotoxicity for highly effective depletion of B cells in patients with refractory autoimmune diseases. In this lecture, I cover the development history of T cell engagers, emerging data in patients with autoimmune disease and theoretical and practical considerations for their design and use. Finally, I review emerging approaches for cell depletion and emerging targets.

The antibody molecule is a wonder of nature that connects disease targets with immune effector cells via its Y-shaped topology of three domains connected by a hinge region. We describe GEM-DIMER technology allowing us to create superdimers of two antibodies interconnected at their hinge regions by a strong non-covalent interaction. Our superdimers demonstrate cooperative binding to disease targets and immune effector cell receptors, making them ideal for human therapeutic applications.

Targeted therapy with covalent inhibitors of oncoprotein KRAS(G12C) are initially effective but typically lack durability due to cancer cell resistance. MHC presentation of the covalently modified KRAS(G12C) peptides on the cell surface creates synthetic neoantigens that can be stabilized and targeted by antibodies across HLA restriction. Conversion to T-cell engagers affords a unique combination of targeted and immune therapy.

This topic explores the revolutionary potential of the genome-edited mouse, where endogenous VH and VL genes are replaced by fully human VH and VL genes in situ, enabling the generation of fully human antibody molecules. When combined with Biointron's AbDrop microfluidic technology-enhanced single B cell screening, this approach allows for the high-throughput and efficient discovery of antibody drug molecules.

We have discovered and characterized the first-ever Nanobodies that act as positive allosteric modulators (PAMs) of clinically relevant inhibitory immune checkpoint complexes (ICCs) that enhance receptor signaling with pathway-specific and spatio-temporal precision. Such ICC PAMs open up novel therapeutic modes of intervention that ensure patient safety, even in cases of overdose, and may outperform current inhibitor-based immunotherapies, which often cause significant side effects.

We are investigating unique payloads by exploring agents that target cancer cell dependencies/vulnerabilities, or that have known or assumed safety liabilities or poor physicochemical properties that would benefit from delivery via antibodies. We will discuss early achievements in the development of these more targeted ADCs.

We have identified B cells with anti-checkpoint specificity in a subset of pre-surgical, untreated lung cancer patients. Upon single cell sorting, sequencing and reconstruction of specific BCRs, we show that these are mostly peripheral memory B cells, encoding antibodies with highly mutated CDRs, and can exhibit checkpoint blocking activity.

Despite the curative potential of cancer immunotherapy, most patients do not benefit from existing treatments. Glyco-immune checkpoints – interactions of cancer glycans with inhibitory glycan-binding receptors called lectins – have emerged as prominent mechanisms of resistance to molecular and cellular immunotherapies. I will describe development of antibody-lectin chimeras: a biologic framework for glyco-immune checkpoint blockade that is now moving toward the clinic.

Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk remain unexplored, and there are currently no approved treatments that directly target cardiac fibrosis. Using human tissues and mouse models, we delineate the functions of FAP+ fibroblasts within the heart and define immune cell crosstalk and transcriptional events that govern their differentiation. From a broader perspective, we show that bispecific T-cell engaging antibodies targeting FAP+ fibroblasts suppress cardiac fibrosis and have similar effects in other organs. These findings highlight the therapeutic potential of cell specific targeting of defined fibroblasts subsets.

The development, delivery, and efficacy of therapeutic antibodies are strongly influenced by multiple types of molecular interactions mediated by their variable regions, including both specific and non-specific interactions. Here we report interpretable machine-learning models for identifying high-affinity mAbs with optimal combinations of low off-target binding and low self-association, and demonstrate that these co-optimal antibodies display drug-like properties both in vitro and in vivo.

This presentation will explore how Adimab has revolutionized antibody discovery, growing from an innovative startup into a leading platform technology company. We will examine key technological breakthroughs in our platform, focusing on synthetic antibody library evolution, advances in multispecific generation, and novel approaches to developability optimization. Join us to learn how Adimab's engineering-driven approach is shaping the future of therapeutics.

Bispecific T cell engagers (TcEs) must create an effective immunological synapse, yet how their structural features control potency is poorly defined. We combined solution structural analyses and synapse imaging on supported lipid bilayers to show that both intermembrane distance and complex rigidity critically determine TcE activity. Formats producing close contacts and reduced molecular flexibility enhanced co-stimulatory interactions and cytotoxic responses. These findings provide actionable design principles for next-generation TcE therapeutics.

The efficiency of complement activation among IgG subclasses is primarily determined by their capacity to form oligomers upon binding to antigens. This oligomerization facilitates the multivalent engagement of the C1 complex, thereby initiating the classical complement pathway. These insights offer a mechanistic understanding that could inform the design of antibody therapies with enhanced effector functions.

Antibodies discovered in vivo have many advantages such as high affinity and low polyspecificity/reactivity with superior developability profiles compared with those identified through in vitro methods. However, immunization-driven approaches have historically faced challenges with complex targets that are evolutionarily conserved. We present a case study in which genetic immunization successfully generated a panel of antibodies against a 100% conserved, multi-subunit, cell-surface heterocomplex, and the epitope diversity was revealed through in silico mapping. This study highlights that breaking tolerance in mice can be effectively achieved and integration of in silico tools facilitate rapid decision making for downstream lead selection.

Over the last several years, China has rapidly emerged as a leader in global drug development, now surpassing the US in the number of active clinical trials. This advancement is the result of a decade long Chinese national strategy to invest in and develop a leading biopharmaceutical industry. The implications of these changes for US biotech and biopharma will be discussed.

The ion channel Kv1.3 is well known to be important in the activation of effector-memory T cells. We have developed a unique ultralong CDR3 antibody based on the cow scaffold that potently inhibits Kv1.3 activity. Surprisingly, this reagent was also found to inhibit important immune functions in monocytes and macrophages, revealing a novel role for Kv1.3 in the innate immune system.

PRO-XTEN™ masked T cell engagers (TCEs) are conditionally activated immune therapeutics designed to exploit dysregulated protease activity within the tumor microenvironment. This approach enables tumor-selective TCE activation while minimizing systemic toxicity. The XTEN mask serves a dual function: masking TCE activity and extending the half-life of the masked molecule, while the proteolytically activated TCE exhibits a short half-life, creating conditional pharmacokinetics that enhance tumor exposure while limiting systemic active drug circulation. Preclinical studies demonstrated: (1) robust masking with ~10,000-fold reduction in cytotoxicity in vitro; (2) potent anti-tumor efficacy in vivo at doses comparable to unmasked TCE controls; and (3) >100-fold improvement in maximum tolerated dose (MTD) in non-human primates. These findings support a significantly enhanced therapeutic window through tumor-specific activation and conditional PK. Clinical trials evaluating PRO-XTEN™ TCEs targeting HER2, PSMA, and EGFR are currently underway, with early data demonstrating the translational potential of this protease-activated platform.

Next-gen immunotherapies demand seamless integration of multimodal data—sequence, structure, assay, and biophysical insights. Traditional tools can’t keep pace. This talk introduces a new paradigm: a Multimodal Scientific Intelligence Platform built to unify antibody/protein workflows, enhance collaboration, and accelerate AI-ready discovery. Includes a case study from a major biopharma showing how multimodal workflows improve outcomes in multispecific antibody engineering.

PRO-XTEN^TM masked T cell engagers (TCEs) are conditionally active by exploiting the dysregulated protease activity in tumors. Preclinically, PRO-XTEN^TM TCEs demonstrated 1) Strong masking of in vitro cytotoxicity by approximately 4 logs; 2) Potent in vivo efficacy at doses similar to the efficacious doses of unmasked TCE controls; and 3) Increased MTDs in NHP by greater than >100 fold. Clinical trials of PRO-XTEN TCEs targeting HER2, PSMA and EGFR are currently ongoing.

We have commenced efforts to engineer knottins and cyclins as general-purpose binders for a variety of applications where their rugged durability would be enabling (e.g. oral delivery, cytoplasmic delivery, radioligand therapy). Occupying a parameter space intermediate between antibodies and small molecule drugs, these molecules present new challenges and opportunities for protein engineering.

The inability of diverse biomolecules to readily penetrate the blood-brain barrier is a key limitation to their use in research, diagnostic, and therapeutic applications. We are developing bispecific antibodies that engage either CD98hc or transferrin receptor, and efficiently transport biomolecules into the CNS. We will discuss our recent work on protein delivery to the CNS, including cytokines for modulating the immune environment in the brain for therapeutic applications.

Radiotherapy remains a cornerstone of cancer treatment, yet its efficacy is often limited by normal tissue toxicity and tumor resistance. This talk will highlight a translational strategy to enhance radiotherapy by leveraging antibody-drug conjugates (ADCs) for targeted delivery of cytotoxic agents. I will present preclinical data demonstrating how ADCs directed against radiation-inducible tumor antigens potentiate tumor response, offering a precision-based approach to improve outcomes in solid tumors.

New antibody therapies span a wide range of indications with varying development costs and complexity. Partnering programs validates technology platforms, brings resources to bear, and raises funds, but dilutes ownership and long-term value. Novel antibody case studies from a range of program development stages and company sizes will be critically discussed.

Despite advances in cancer therapeutics, new protein targets and targeting approaches for drug development are needed. We developed a high-resolution proximity labeling technology using photocatalyst-generated reactive probes to label discrete cell surface protein microenvironments. Utilizing our platform to identify proteins inherently proximal to EGFR, we identified CDCP1. This led to the development of IDP-001, a novel bispecific ADC targeting EGFR and CDCP1. Identification and characterization of IDP-001 will be presented.

Generative AI is redefining what’s possible in biologics discovery — enabling scientists to explore protein sequence space more efficiently, design higher-performing molecules, and accelerate the path from concept to candidate. At Cradle, we are developing intuitive software tools that allow protein engineers to directly leverage generative AI models within their existing workflows. This presentation will showcase how Cradle’s technology enables scalable and reproducible protein design, combining advanced AI architectures with user-centered design to reduce cycle times and ultimately create better biologics.

Influenza A viruses pose a persistent public health challenge due to antigenic diversity, rapid evolution, and zoonotic reservoirs with pandemic potential, as highlighted by recent H5N1 spillover from cattle to humans. Immune history shaped by repeated exposure complicates both prevention and therapy. We show how isolating and functionally characterizing human hemagglutinin-targeting antibodies reveals cross-reactive immunity, identifies conserved vulnerabilities, and informs strategies for antibody-based therapeutics and vaccine design.

Mabylon’s allergy pipeline leverages naturally occurring human antibodies to generate multispecific therapeutics targeting disease‑relevant allergen epitopes. Lead candidate MY006, a tri‑specific anti‑peanut antibody designed for low‑frequency dosing, blocks IgE binding and suppresses allergic effector‑cell activation, and is currently under investigation in Phase 1 studies. The broader pipeline applies the same discovery engine to additional food and environmental allergens, including birch allergy, with the potential to fundamentally transform allergy treatment.

The patent landscape for antibody therapeutics is rapidly evolving, with overlapping technologies and filings leading to complex freedom-to-operate issues as well as increasingly higher hurdles to obtaining patent protection. Developing robust patent estates that meet this challenging legal environment can be a key to success. Strategies for navigating this environment will be discussed.

DPBIO’s CytoSpark® system enables rapid, high-throughput screening of single plasma B cells for monoclonal antibody discovery. Supporting diverse species including rabbit, mouse, alpaca, and human, CytoSpark® delivers functional screening for challenging targets like membrane proteins and GPCRs. With single-cell precision and functional relevance, it also supports enzyme evolution and synthetic biology, accelerating timelines and expanding the frontier of biologics discovery.

Respiratory syncytial virus (RSV) causes a substantial respiratory disease burden in older adults. Three vaccines, each based on a prefusion-stabilized RSV F antigen, have now been licensed. Here, we delineate the humoral response elicited by Moderna’s RSV mRNA vaccine, characterizing antibody responses at both the polyclonal serum and single-B-cell levels.

Using an entirely original strategy, we have developed a novel platform that uses dual-binding antibodies to generate therapeutics with targeted, conditional activity only when bound to a selected marker. We are currently applying this Antibody Controlled Therapeutic technology to multiple targets, including PD1, LAG3, ATP, and LRRC15 and to multiple effectors including IL-2, IFN-a, IL-12 and TGFb inhibition.

Celiac disease is an autoimmune disorder in which ingestion of gluten damages the small intestine in genetically predisposed patients carrying HLA-DQ2.5 haplotype. DONQ52 is a novel neutralizing antibody that exhibits broad cross-reactivity against multiple gluten peptide/HLA-DQ2.5 complexes. In this presentation, we will present the identification of the lead antibody, its multidimensional optimization process, and the key characteristics of DONQ52.

The conditions for Plasmids, Transient HEK293 and Transient/Stable CHO from 96 well, 24 well, 6 well, 125mL-7L Optimum Growth flasks need to be maintained at small scale. Data will be presented on techniques and technology that allow for getting high amounts of protein in smaller volumes with fast techniques from 1mL-3L. This allows teams to get to IND molecules quickly. All of these techniques are proven technologies for protein production, structural biology, and can lead to successful clinical candidates.

Plasmodium falciparum malaria remains a global health problem. Here, I will discuss our efforts to identify and characterize human antibodies against Plasmodium falciparum targets including their clonal evolution and target epitopes to inform the development of improved malaria vaccines.

High-quality therapeutic antibodies aren’t the product of a single experiment, but of a series of cross-validated decisions spanning the entire drug discovery process. In this talk, Mosaic shares practical lessons from running quality-first, fit-for-purpose discovery – programs that blend in vivo and in vitro approaches to deliver candidates that work in the real world. Rather than showcasing a single case study, we’ll walk stage-by-stage through the discovery workflow, and at each stage, we’ll present a short case study: the stubborn problem we hit, what didn’t work, the tactic(s) that did, and a concrete rule of thumb you can reuse to avoid similar roadblocks in the future.

At NonaBio we are innovating away from simply screening for antibodies based on binding affinities and developing more novel early-stage function-based screening platforms. This presentation highlights examples of function-based screening of VH sequences generated from our fully human heavy chain only HCAb Harbour Mice® discovery platform.

I will discuss SureTACs technology that we developed for targeted degradation of transmembrane proteins, utilizing heterobifunctional antibodies that mediate induced proximity of a transmembrane E3 ubiquitin ligase and the target. Upon tethering E3 to target, the target protein undergoes ubiquitination, endocytosis and lysosomal degradation. I will discuss how we identify optimal E3-target combinations and share proof-of-principle and in vivo efficacy data for PD-L1-targeting SureTACs.

While there has been substantial innovation in bispecific engineering, approaches to bispecific discovery have thus far been cursory, often narrowly focused on pre-determined target pairs of known biology. Dualitas has built a bispecific discovery engine that operates at combinatorial scale, enabling functional screening of cell surfaceomes at vast target and epitope space. Large unbiased screens have illuminated novel co-target biology and yielded an emerging bispecific pipeline of I&I programs with differentiated activities unachievable by conventional inhibitors. Concomitantly, observations of repeatable activities are elucidating a novel collection of immune engagers, plug-and-playable mechanisms and antibody arms that can bring superior pharmacology to established therapeutic pathways.

This talk will share updates from the AIntibody competition, a benchmarking initiative engaging the biotech, pharma, academia, and AI communities to use AI and other informatic methods to design or identify developable antibodies with high affinities, from curated NGS datasets. Results will compare the properties of these antibodies with those derived using experimental methods, providing insights into the value of AI in antibody discovery. AIntibody announcement manuscript: Erasmus, M. F. et al. Nat Biotechnol 42, 1637-1642 (2024).

We present Germinal, a model for performing epitope-targeted design of de novo nanobodies and scFvs against a wide range of epitopes, including the ability to design specificity or breadth across multiple targets.

Our fully integrated AbZelectPRO™ platform enables the rapid delivery of stable, high-producing cell lines to support the production of antibodies and more difficult-to-express proteins. The platform combines our AbZelectPRO™ CHO-K1 and AbZelectPRO™-KO GS knockout cell lines together with ProteoNic’s 2G UNic® vector technology and, supported by our comprehensive analytics capabilities, provides a state-of-the-art offering to support our clients as they transition from R&D into preclinical and clinical development.

TAVO412 is an avidity driven trispecific antibody that engages multiple mechanisms of action to control different resistance mechanisms in solid tumors. We describe confirmation of target engagement in Phase 1A trials for patients struggling with mutant lung, esophageal, and colorectal cancers. In addition, we highlight the pharmacokinetic profiles, tolerability, and clinical responses.

As a critical step towards uncovering the extent and functional consequences of germline-encoded variation in adaptive immune receptor genes, we developed an ultra-high throughput multiplexed sequencing technique, ImmuneDiscover. This approach allows individualized immunoglobulin (IG) genotyping from nanogram quantities of genomic DNA and multiplexing >1,000 individuals in a single analysis. We benchmarked the approach on 90 donors from different population groups and subsequently genotyped 2,486 cases from the Thousand Genomes Project (1KGP) collection, creating an atlas of human IG gene variation, KIARVA. All alleles were validated against existing SNP databases from >million individuals using IgSNPer. We found extensive population differences in IG genes known to be important in pathogen responses, including a homozygous multigene IGHD segment deletion present in up to 30% of East Asian individuals. In addition, we show evidence of disease responsive haplotypic differences in human population groups, suggesting localized selection pressures, and illuminate ongoing genomic processes that function to maintain IGH locus heterogeneity.

Despite advances in cancer therapeutics, new protein targets and targeting approaches for drug development are needed. We developed a high-resolution proximity proteomics technology using photocatalyst-generated reactive probes to label discrete cell surface protein microenvironments. Combined with quantitative mass spectrometry, we characterize plasma membrane protein interactomes and integrate proximity proteomics data with clinical protein expression profiles through computational graphs and graph convolutional neural networks (GCNNs). This membrane interactomics (MInt) database enables the unbiased identification of inherently proximal surface antigens in tumor microenvironments and facilitates precise dual-targeting of malignant cells. Utilizing our platform to identify proteins inherently proximal to EGFR on tumor cells, we identified CDCP1 as a TAPA (tumor associated proximity antigen) of interest. Our findings led to the development of IDP-001, a novel bispecific ADC targeting EGFR and CDCP1, anticipated to enter clinical trials in 2026. Identification and characterization of IDP-001 will be presented.

Ficerafusp alfa, is a first-in-class EGFR-TGF-b bifunctional antibody. TGF-β signaling within the tumor microenvironment (TME) creates fibrotic, immunosuppressive barriers that impede tumor penetration of immune cells. Mechanistic insights from paired biopsies and preclinical studies reveal the importance of tumor targeted inhibition of TGF- b in breaking down barriers to tumor penetration. Ultimately, ficerafusp alfa’s tumor penetration has the potential to drive deep and durable responses that lead to long-term clinical benefits.

Therapeutic protein engineering has been transformed by the incorporation of big data and AI/ML techniques. An emerging challenge for this field is how to efficiently leverage the right data and the best models to drive meaningful results and resolve long-standing bottlenecks. Amgen has incorporated a generative biology approach to tackle complex engineering problems, aiming to deliver better, more effective molecules across every therapeutic program.

Autoantigen-specific IgA autoantibodies correlate with disease severity in autoimmune and fibrotic diseases. The presence IgA/autoantigen immune complexes result in continuous CD89-mediated activation of myeloid cells, leading to severe tissue damage. Activation of myeloid cells is a highly underappreciated and untargeted in autoimmune diseases. We developed an antagonist humanized anti-CD89 antibody (JJP-1212), that by interfering with the IgA/CD89 axis, resolves IgA/autoantigen-induced inflammation and subsequent tissue damage in autoimmune and fibrotic diseases.

Serological antibodies represent an immunologically distinct compartment from B-cell repertoires that is often overlooked by genetic methods. A novel proteomics platform enables standalone protein-level discovery from complex human serum, sequencing unique antibodies absent in B-cell data. In a COVID-19 benchmark with zero prior B-cell neutralizers, we identified 18 distinct clones, yielding 8 neutralizers (3 highly potent, <0.2 µg/mL IC50), facilitating a pathway to real-world therapeutic discovery across diseases.

Immune organoids model key features of human adaptive immunity, including antigen-specific antibody responses. Immune organoids are derived from lymphoid tissues and recapitulate the diversity of human immune responses. This talk will discuss the utility of the organoid model for investigating host and antigen format factors that influence the magnitude and quality of the antibody response.

Antibodies bridge innate and adaptive immunity through their constant (Fc) domains, yet most of Fc functional space remains unexplored due to experimental constraints. To address this, we developed an AI-guided platform for Fc-engineering. By integrating the screening of synthetic Fc-libraries with next-generation sequencing and deep learning, we built FcGPT – a protein language model that designs antibody Fc-variants with bespoke Fc-receptor binding profiles, unlocking new possibilities for antibody design and immunotherapy.

Standard bioassays often fall short when evaluating immune-modulating biologics due to their complex and diverse MOAs. This presentation explores the use of context-specific in vitro models for T cell engagers in oncology and biologics targeting autoimmune pathways. Through case studies, we highlight how tailored assays, such as T cell activation, cytokine release, and target-specific inhibition, enable robust assessment of drug potency, specificity, and mechanism of action.

Monoclonal antibodies have recently been shown to prevent malaria in clinical trials in endemic regions, but challenges remain regarding antibody cost, potency, and specificity. Here, we describe the discovery of next-generation antibodies that target the malaria parasite, Plasmodium falciparum, as part of efforts to develop new anti-malarial vaccines and prophylactics.

Antibody engineering is evolving, and Gibson SOLA delivers the synthesis technology to match. This modular enzymatic platform enables rapid, on-demand production of antibody variants using conserved sequences, allowing more candidates per screen and fewer iteration cycles. From scFvs to Fc-fusions, SOLA empowers deeper campaigns, faster decisions, and unique discovery strategies—all at comparable or reduced cost, without outsourcing delays.

This presentation will explore how Adimab has revolutionized antibody discovery, growing from an innovative startup into a leading platform technology company. We will examine key technological breakthroughs in our platform, focusing on synthetic antibody library evolution, advances in multispecific generation, and novel approaches to developability optimization. Join us to learn how Adimab's engineering-driven approach is shaping the future of therapeutics.

Standard bioassays often fail to capture the complexity of immune modulating biologics. This presentation examines the use of context specific in vitro models for T cell engagers in oncology and autoimmune therapies. Through representative case studies, we demonstrate how tailored assays including T cell activation, cytokine release, and target specific inhibition provide robust insights into drug potency, specificity, and mechanism of action, supporting more informed, data driven decision making in biologic development.

Immunogenicity is a major challenge in biologic drug development, compromising efficacy and safety. Our ADAx platform selectively suppresses B cell activation against therapeutics while preserving normal immune function and drug activity. It enables strong ADA suppression and improved pharmacokinetics in vivo, offering a versatile solution across protein and antibody formats.

OptiMAL™ represents the World's first platform using a fully synthetic human antibody library that can be screened using Mammalian Display in the native IgG format. The results shown will demonstrate that this platform can be used for the discovery of antibodies with high specificity, developability and yield, in a competitive timeframe. Followed by the knowledge that a rationally designed synthetic library can out-perform more traditional library design methods.

PIP is a versatile targeting peptide that binds selectively to multiple tumor-associated targets, a unique feature enabling payload delivery to virtually any solid tumor. This presentation focuses on the development of PIP-Drug Conjugates, their efficacy and safety, and how PIP’s multi-specific targeting overcomes resistance seen with conventional single-antigen targeting ADCs.

Developability assessment remains a bottleneck in early antibody discovery. PAIA´s plate-based developability assay platform provides a fast and easy-to-automate way to characterize hundreds of thousands of molecules per day.

In this presentation we show developability data for different sample sets of mAbs, VHH-Fc Fusions and bispecifics and compare the results with orthogonal methods and published data.

Neonatal Fc receptor is a popular target for treatment of autoimmune disorders due to its role in maintaining IgG levels. Fc-ABDEG and albumin-binding VHH were combined to develop next-generation FcRn blockers with improved IgG clearence. Step-wise engineering was applied to optimize position and number of VHHs, their affinity to albumin, and the linker connecting it to Fc-ABDEG. Novel FcRn-based cellular assays and human FcRn transgenic mice will also be addressed.

EpiTACs are bispecific antibodies in which one arm binds a pathogenic target, and the other arm leverage tissue-enriched degrading receptors to selectively degrade a wide range of extracellular targets including membrane, soluble, and multi-span proteins. EpiTACs to multiple oncology and autoimmune targets demonstrate that target degradation drives compelling in vivo activity. EpiTACs can also deliver ADC payloads creating novel therapeutics that combines target degradation with ADC cytotoxicity. The dual mechanism of EpiTAC ADCs leads to anti-tumor activity that outpaces current standard of care molecules.

Melanocortin receptor 4 (MC4R), a class A GPCR, suppresses appetite upon activation, but current peptide agonists lack receptor selectivity. Using Confo technology, we stabilized active-state MC4R with a conformation-selective ConfoBody to discover potent, MC4R-specific VHH agonists. We identified the most potent VHH and resolved its structure bound to the orthosteric pocket. This highly specific VHH offers a promising candidate for selective anti-obesity therapy via MC4R activation.

Antibodies have broad utility in imaging, targeted gene delivery, and disease therapy, and many of these applications require conjugation to secondary molecules. Unfortunately, conventional conjugation approaches are limited by destabilization of structure, heterogeneity, and technically demanding multi-step reactions. To overcome these challenges, we developed a straightforward and highly general platform for site-specific antibody conjugation that blends metabolic glycoengineering with protein design, presenting a highly efficient strategy to produce antibody conjugates.

We ran an open protein design competition in where 100+ participants from industry and academia submitted binders against Nipah virus. Testing 1000 sequences experimentally in our lab revealed which computational methods translate to experimental success, with hit rates varying 10-fold between approaches. We'll share lessons on benchmarking design pipelines, the value of negative data, and how open competitions can accelerate the field when paired with standardized experimental validation.

Systemic toxicities from target expression on healthy tissues limit cancer therapy. The PrimeBody platform employs protease-cleavable linkers and affinity-tuned masking to generate tumor-activated biologics with exceptional systemic stability and efficient tumor activation. VOR-101, a masked, Fc-enhanced CD47 blocker, remains inert in circulation but rapidly activates in tumors, achieving >700-fold selectivity. It delivers ~100-fold higher exposure than conventional agents without toxicity, driving durable tumor regressions and a markedly improved therapeutic index.

We are developing dual-payload ADCs that enable delivery of two different payloads simultaneously to the tumor with the goal of enhancing therapeutic efficacy and overcoming resistance mechanisms. Leveraging our cell-free platform, we precisely control payload placement and ratio to optimize efficacy. Preclinical data demonstrate superior efficacy in vitro and in vivo over single-payload ADCs, with favorable pharmacokinetics, stability, and safety.

Are you within 10 years of completing your Master’s or Ph.D. and under the age of 35? If so, unlock a range of exclusive benefits by selecting the "Early Career Scientist" pass when you register. This session will spotlight short, novel research presentations from early career scientists in the antibody engineering and therapeutics community. You’ll also hear an inspiring career journey from a distinguished mid-career scientist, plus enjoy the opportunity to connect and network with peers. You’ll also receive free admission to the afternoon pre-conferences workshops on December and the opportunity to present a free poster during the main conference. Please Note: Access to the early career scientists session is only available to those who register for the main conference by selecting the “Early Career Scientist” pass. All passes subject to approval by conference organizers.

To be considered for a short oral presentation in this session, or for general information about this session, please contact Michael Keenan at Michael.keenan@informa.com

If you are interested in sponsoring this session, please contact Blake Shuka at Blake.Shuka@informa.com

Monkeypox is a dangerous virus, and some of its key targets for immunity are still unknown. We discovered antibodies that recognize a viral protein called A28 and showed they can strongly neutralize Monkeypox and related viruses. Vaccinating mice with A28 triggered powerful immune responses and fully protected them from infection. These results suggest A28 could improve future Monkeypox vaccines.

Trispecific antibodies (tsAbs) can bind three distinct targets, enabling next-generation approaches in areas like cancer therapy. By engaging multiple tumor-associated antigens, tsAbs can increase tumor specificity, limit antigen escape, and enhance immunostimulatory effects compared to bispecific or monospecific antibodies. We present data on the T-body, a Fab-based, IgG-like trispecific antibody platform with high expression, efficient assembly and good developability characteristics, which accelerates and de-risks development of innovative immunotherapies.

Maxion have shown that small cysteine-rich peptides (“knottins”) with ion-channel modulating activity can be inserted into antibody CDR loops while retaining their function. The resulting “KnotBody molecules modulate ion channel activity while benefitting from the optimal drug-like properties of antibodies. This presentation will illustrate the generation and optimisation of KnotBody inhibitors of Kv1.3, an important ion channel affecting function of T effector memory cells.

We present discovery of a novel IgE cleaving protease engineered using our proprietary machine learning enabled IMPACT platform to obtain desired target specificity, potent cleavage, and efficacy in preclinical models with favorable manufacturability properties, low immunogenicity, pharmacokinetics, and pharmacodynamics. IgE cleavers offer a new potential targeted therapy for allergic and atopic diseases.

Immunostimulatory antibodies targeting immune receptors represent an exciting new modality for immunotherapy. Using TNFR superfamily receptors as a paradigm the role of isotype, epitope and affinity have previously been explored. Recently, the modification of the antibody hinge has been investigated as a hitherto unexplored means to tune and mediate powerful receptor agonism. The various approaches to exploit the hinge will be presented.

Natriuretic peptide receptor 1 (NPR1) is a membrane-bound guanylate cyclase and activated by atrial (ANP) and brain (BNP) natriuretic peptide and NPR1 agonism alters blood pressure via regulation of intravascular volume, vasorelaxation, natriuresis and diuresis. We have isolated fully human antibodies from VelocImmune® mice that either agonize or antagonize NPR1 activity and are developing as potential treatment of cardiac diseases such as heart failure and hypovolemic/hypotensive disorders.

The rapid expansion of complex biologics—bispecifics, multispecifics, Fc-fusions, has exacerbated the disconnect between early discovery expression systems and manufacturability. The CHO Edge Rapid Pools addresses this developability gap by providing discovery teams with CMC-grade pools and molecule insights early enough to influence lead optimization, architecture selection, and manufacturability assessments.

Immunogenicity of biopharmaceuticals can affect their safety and efficacy. Mitigation of this risk should start early in development, at the drug design phase. This presentation discusses incorporating advanced in silico and in vitro de-immunisation tools into protein engineering processes to select a lead candidate that balances immunogenicity risk and desired biophysical properties.

Developed by the team behind Sc2.0’s synthetic yeast genome, neoSwitch is a yeast strain that flips between surface display and secretion with a simple media change—eliminating antibody reformatting and host switching. Neo offers high-diversity naïve VHH and scFv libraries (>10^9) for rapid, first-pass discovery, and we routinely design, build, and transform custom libraries for partners. Paired with the Opentrons Flex, neoSwitch enables turnkey, automatable workflows—including protein purification—to accelerate hit-to-lead.

Speaker #1: Next-Gen BsAb Manufacturing: How TurboCHO Ensures High Productivity & Purity in Manufacturing
This presentation will introduce GenScript’s TurboCHO™ technology, an integrated, DOE-driven workflow that optimizes cell lines, vectors, and media to fine-tune chain ratios and boost yields. A streamlined, customizable purification strategy using advanced chromatography further improves product purity.

Speaker #2: Structure First Approaches to Vaccine and Antibody Design

Rational vaccine design is predicated on a deep molecular understanding of epitope-paratope interactions between antibodies and cognate antigens. Generating these data can be quite laborious, time consuming, and at great cost. To accelerate this process we developed a hybrid structural and bioinformatic approach to directly assign the heavy and light chains, identify complementarity-determining regions and discover antibody sequences from cryoEM density maps of serum-derived polyclonal antibodies bound to an antigen. When combined with next generation sequencing of immune repertoires we can specifically identify clonal family members, synthesize the monoclonal antibodies and validate their binding interactions. This structure-based approach for identification of monoclonal antibodies from polyclonal sera opens new avenues for analysis of immune responses, iterative vaccine design, and monoclonal antibody discovery. Continuous technological developments such as automation of data processing and structure interpretation as well as assay miniaturization further increase the throughput and accessibility of our approach.

neoSwitch^TM is a yeast strain engineered to toggle between display for antibody library screening and secretion for 5-100 mg/mL VHH/ScFv production. By combining 10⁹-member synthetic or semi-synthetic libraries with turnkey Opentrons Flex^TM automation and the Goldilocks Libraries^TM affinity-maturation workflow, it is possible to isolate monomeric VHHs with picomolar binding affinities in weeks.

Since the first ADC approval 25 years ago, the MMAE vedotin platform has been the most widely utilized. Over 50 targets have been paired as vedotin ADCs and tested across heme and solid tumors, offering a rare opportunity to leverage insights about ADC target selection. Recent vedotin ADC NSCLC clinical data suggest that targets with unique biology, such as PD-L1 and Integrin Beta-6, are enabling success in a tumor type where other vedotin ADCs have failed.