ON-DEMAND PRESENTATIONS

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.

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.

Recent breakthroughs in cancer immunotherapy have highlighted the potential of leveraging natural killer (NK) cells for cancer treatment, with NK cell engagers (NKCEs) emerging as a promising strategy. We will present the discovery of a panel of Nkp80 engagers, and the subsequent engineering of a trifunctional NKCE that targets HER2 on cancer cells while engaging Nkp80 and CD16a on NK cells (HER2-NKCE). HER2-NKCE demonstrated potent antitumor activity against HER2-positive cancer cells, with picomolar-range potency. It effectively targeted a range of HER2 expression levels, inducing NK cell activation and cytokine secretion exclusively in the presence of HER2-expressing cancer cells, significantly outperforming the HER2 antibody Trastuzumab. Moreover, the dual-engagement of Nkp80 and CD16a led to a robust immune response. Importantly, HER2-NKCE exhibited target-dependent cytotoxicity against cancer cells, while sparing HER2-positve normal cells, thereby minimising on-target off-tumor effect.

Abalone Bio’s Functional Antibody Selection Technology (FAST) platform is driven by a powerful combination of large-scale activity measurement and machine learning (ML) to identify and design activating antibody drugs against challenging targets. In combination with Abalone’s developability ML models, this enables the design of novel, therapeutically active and highly developable antibody sequences. Agonists for multiple GPCRs, including CB2, were identified using FAST, which have macrophage-modulating, anti-inflammatory activities in vitro and ex vivo in human precision-cut liver slices, and therapeutic activity in animal models of neuropathic pain and advanced liver cirrhosis. These antibodies activate their target through non-orthosteric mechanisms involving novel binding-function relationships that would have been difficult to discover without using large-scale activity-first selection methods like Abalone’s FAST platform.

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.

The development of antibody-based medicines can be accelerated by enhancing both our understanding and predictive power of antibody-antigen binding. For both purposes, affinity datasets from mutational scans are an important resource, but the factors driving affinity remain insufficiently understood. To address this, we present a multi-modal dataset of antigen and VHH interface variants, that captures changes in binding affinity, protein stability, and expression levels. We observe that the affinity change introduced by most mutations is largely explained by changes in stability rather than interaction-specific effects. Using this data, we confirm that structure-conditioned inverse folding models perform well in predicting the relative stability of protein variants. Finally, we quantify the ability of inverse folding models to capture interface changes of paratope variants and detect little predictive power for the interface changes in epitope variants. Our findings highlight the importance of high-quality, information rich datasets in advancing protein engineering efforts.

We present JAM, a protein design system capable of designing antibodies de novo with therapeutic-grade affinities, function, and early-stage developability for soluble and multipass membrane protein targets. For GPCRs, we show de novo designed antibodies have single-digit nM to picomolar binding affinities, and while most are functional antagonists, remarkably, a subset are agonists -- marking an important milestone in the field.

We will present our practical, platform-driven strategies for generating POC-stage antibodies targeting emerging targets in chronic diseases and oncology. These innovative antibody candidates have the potential to de-risk drug development and address unmet patient needs. Leveraging AI-powered platforms, we enable the discovery and engineering of next-generation antibodies with distinct mechanisms of action, novel modalities, and optimized drug-like properties.

Etcembly is the first company to leverage generative AI to discover and engineer T cell receptor (TCR) biologics for cancer immunotherapy. Using our proprietary machine learning platform, EMLyTM, we predicted the TCR-pHLA interface from sequence alone, leading to the discovery of our lead molecule, ETC-101, a TCR that recognises the PRAME cancer antigen peptide in complex with HLA-A*02. We show that ETC-101, which was designed in silico, was able to signal effectively to elicit T cell activation when expressed as a full-length TCR and was specific to its target peptide. Further predictions from EMLyTM enabled rapid affinity enhancement of the parent molecule by >5 million-fold, resulting in an ETC-101 TCR variant with picomolar affinity. When this high affinity variant was expressed as a bispecific T cell engager, ETCer (Etcembly’s T Cell Engaging Receptor), ETC-101 exhibited strong efficacy and was able to induce robust T cell-mediated cytotoxicity against a panel of target cancer cells. Early preclinical assessment and cross-reactivity screening of the ETC-101 ETCer also demonstrated a promising safety profile, and the suitability of this candidate TCR for advancement into translational development. Our data validates the strong predictive capability of our AI platform EMLyTM in TCR discovery and engineering. Functional characterisation of our lead TCR molecule ETC-101 demonstrates its potential as a novel drug candidate for the treatment of PRAME-positive cancer indications.

This talk will explore cutting-edge strategies for antibody display selections, highlighting their impact on the discovery of novel potential therapeutics, for established and novel format of antibodies: from Fab to VHH. The presentation will cover advancements in display technology approaches to optimize the selection of antibodies with precise features, presenting case studies demonstrating successful applications (e.g., anti-ID, pH sensitivity, specific epitope recognition). Future directions and unmet needs in the field to accelerate precision medicine and the development of new therapies will also be covered.

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.

Quick feedback on what people designed and produced and how these act in the system is essential for the development of novel molecules and formats, but this is challenging. Rigaku developed a 'Molecular projector, MoleQlyze' that can image large molecules and complexes in a solution without prerequisite information and crystallization/freezing/fixation/labeling processes. This enables overnight direct epitope mapping, molecular defects and aging monitoring during culture and purification processes, nucleotide-protein quantitation of vector complexes, and observation of defects in particles with the molecular 3D image under given conditions.

For more information about presenting in this session, please contact Michael Keenan at Michael.Keenan@informa.com

A recent clinical trial involving MOv18 IgE, provided tantalising evidence of IgE’s potential for the treatment of cancer. Epsilogen is conducting a phase Ib trial in which translational data will be collated to further understand mechanisms associated with IgE therapy. In addition, Epsilogen has established a pipeline of anti-tumoral IgEs and two novel platforms: bispecific IgE and a hybrid antibody which combines the effector functions of IgE and IgG.

At OmniAb, we build, shape and mine custom, naturally optimized human immune repertoires in divergent species to discover next generation biotherapeutics. Using our high throughput single B cell screening xPloration platform combined with an AI-guided NGS workflow, we identify drug-like leads, bypassing extensive ex-vivo engineering. We show examples of campaigns across various animal platforms that yielded broad and complementary epitope coverage of disparate specific targets, with a range of affinities, and favorable developability characteristics, increasing options for our partners.

Effective and specific non-opioid therapeutics for chronic pain with high efficacy and no side effects are urgently needed. We have reported that mouse scFv95, a small molecule specifically recognizing and blocking P2X4R, is a promising candidate for further characterization and humanization. Nine humanized scFv (hscFv) variants against an extracellullar fragment of human P2X4 were generated via CDR grafting using E. coli production and His-Tag protein purification. Affinity measurement by ELISA and SDS indicates binding affinity in the nanomolar range. More than 2/3 of humanized small molecules showed higher affinity than the parental protein. Octet measurements further revealed the lead HC3-LC3 had binding kinetics of KD = 2.5 × 10–9 M. No endotoxin or in vivo toxicity is noted. Functional validation in vivo in a trigeminal nerve injury model finds reversal of pain related behaviors within two weeks after a single dose (4 mg/kg, intranasal). The details of the development and characterization of a lead P2X4 hscFv HC3-LC3 small molecule provided here constitute an original method whereby durable reversal of nerve injury hypersensitivity can be accomplished. This study opens new avenues for research to develop humanized non-opioid therapeutic interventions for chronic pain.

ADCs and TCEs are important therapeutic modalities. This presentation covers ADC & TCE antibody discovery from BsAb molecular design and antibody discovery platform selection to fit-for-purpose screening and characterization. We share our extensive experience in TCEs, highlighting key considerations for TCE optimization, such as epitope selection, affinity tuning, and PK. For ADCs, we showcase innovative early candidate screening platforms, including high-throughput internalization assays and bio-conjugation, ADC killing and stability assays.

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.

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.

For more information about presenting in this session, please contact Michael Keenan at Michael.Keenan@informa.com

A bispecific ADC targeting EGFR x HER3 was discovered, named PM1300, which has an asymmetric 1+1 IgG-like structure and optimized affinity. This allows for preferential binding to EGFR/HER3 double-positive cancer cells, rather than EGFR single-positive cells. This may significantly contribute to minimizing safety risk that is common for EGFR-targeting agents. Furthermore, this also significantly increased internalization efficiency and in vivo efficacy against EGFR/HER3 double positive tumor compared to 2+2 format ADC indicating a superior therapeutical window.

Amanitin-based ADCs (ATACs) offer a novel mode of action in targeted cancer therapy, distinct from traditional cytotoxic agents. With precisely engineered backbones, they enable the development of highly effective low DAR (Drug-to-Antibody Ratio) species, optimizing stability and therapeutic impact. Amanitin selectively inhibits RNA polymerase II, halting mRNA synthesis and inducing apoptosis. This unique mechanism targets both proliferating and quiescent tumor cells, tackling a key challenge in modern oncology: therapeutic resistance. HDP-101, a BCMA-ATAC, is in a Phase I/IIa trial for relapsed or refractory multiple myeloma. Currently in its sixth cohort, the study has shown promising results, including one complete remission and notable biological activity in several patients. Other ATAC portfolio candidates include HDP-102, an anti-CD37 ADC for non-Hodgkin lymphoma, and HDP-103, an anti-PSMA ADC for prostate cancer, showcasing the platform's versatility in addressing hard-to-treat malignancies.

This presentation will highlight the development of AT65474, a CLDN6-targeting ADC leveraging AxcynDOT™, a novel payload platform with enhanced potency and safety. AT65474 employs site-specific conjugation via AxcynCYS™ technology to achieve highly uniform DAR4 profiles (>97%), improving consistency and efficacy. We will present preclinical data demonstrating potent anti-tumor activity in CLDN6-positive CDX and PDX models, broad in vitro cytotoxicity across drug-resistant lines, and favorable safety in GLP toxicology studies. Key lessons in payload optimization, linker stability, and overcoming regulatory hurdles for IND readiness will also be shared, underscoring our approach to next-generation ADC development.

MabPair is a novel technology for making the next generation antibody combination products that are capable of targeting multiple molecules and pathways. The core technology is based on an antibody engineering platform that enables the production of two full length IgG molecules from a single production cell line. The technology platform can be used to develop therapeutic antibody products that contain a mixture of two different antibodies in a predefine ratio through the conventional antibody manufacture process. MabPair products can offer compelling advantages over bispecific antibodies or conventional antibody combination including abilities to achieve different level of target coverage for the two antibodies, full flexibility in choice of different Fc backbones for antibody effector function and pharmacokinetics profiles, streamlined regulatory and clinical development paths, and single-entity pricing power. Recently our first MabPair product was approved in China by NMPA. The talk will describe the process of generating MabPair products with case studies that highlight the unique feature of the platform and its potential applications in different therapeutic settings.

TfR1 is involved in iron uptake and cell growth. Many cancers express TfR1, but TfR1-targeted agents have safety risks. KK2260 is a REGULGENT™ technology-based bispecific antibody targeting TfR1 and EGFR. KK2260 resulted in EGFR-binding dependent TfR1 downregulation and demonstrated potent anticancer effect against EGFR-expressing tumors. Clinical study is ongoing (NCT06248411).

For more information about presenting in this session, please contact Michael Keenan at Michael.Keenan@informa.com

We present JAM, a protein design system capable of designing antibodies de novo with therapeutic-grade affinities, function, and early-stage developability for soluble and multipass membrane protein targets. For GPCRs, we show de novo designed antibodies have single-digit nM to picomolar binding affinities, and while most are functional antagonists, remarkably, a subset are agonists -- marking an important milestone in the field.

The development of antibody-based therapeutics necessitates precise target engagement to minimize off-target effects and ensure optimal safety profiles. This presentation outlines a systematic de-risking strategy leveraging multiple New Approach Methodologies (NAMs) platforms, with an emphasis on the Retrogenix® Cell Microarray Technology and in vitro safety profiling in both human and non-human primary cells. This comprehensive approach is designed to effectively identify and mitigate potential liabilities.

Machine learning is revolutionizing antibody engineering by leveraging generative AI models that incorporate systematically varied experimental data. Here, we utilize an iterative sparse dataset to affinity mature an antibody while simultaneously minimizing polyreactivity, increasing titer, increasing Tm, and reducing aggregation through multiobjective optimization. This innovative approach bypasses traditional methods, accelerating therapeutic development with precision and efficiency.

Most preclinical models fail to predict the clinical PK of antibodies and related molecules. To develop models for antibody PK studies, The Jackson Laboratory created a series of transgenic humanized models incorporating several genetic modifications. These models were shown to be effective in assessing the clinical half-life of WT and Fc-modified antibodies and allow efficient lead selection and prediction of the clinical PK parameters of therapeutic antibody candidates.

neoSwitch is a yeast strain with the capacity to ‘switch’ between surface display and secretion. Antibody fragments are secreted at high titers in multi-well plates and the raw supernatant is compatible with biolayer interferometry. When combined with the Opentrons Flex, neoSwitch enables turnkey automation of key workflows, including protein purification.

Developability is a critical, yet often overlooked, aspect of the pipeline for therapeutic antibody development. Specifica utilizes highly functional antibody libraries for the identification of developable, drug-like antibodies (IgG or VHH) directly from discoveryor maturation campaigns. In this presentation we describe the latest advances to both our library designs and our pipelines to identify antibody leads with improved developability.

At Hooke Bio, we design tailored fluid flow systems that integrate all your cells of interest, transforming the way immunotherapies are developed and tested.

Powered by our cutting-edge Mera system, we deliver circulating dynamic flow over complex 3D organoid models, allowing for precise assessment of off-target and/or solid tumour effects.

Our advanced in vitro studies, both standard and customized, enable researchers to screen novel therapeutics, uncover mechanisms of action, and accelerate clinical trial design. By identifying safe, effective immunotherapies at the preclinical stage, Mera helps drive more successful treatments, fewer side effects, reduced drug failures, and better disease prediction.

For immunotherapy developers seeking rapid access to next-generation technology, Hooke Bio provides a cost-effective solution—delivering physiologically relevant, human-based immunologic models without the need for expensive equipment.

We also offer a full suite of traditional assays, including flow cytometry, cytokine analysis, and immunochemistry analysis, ensuring comprehensive support for your research.

Accelerate discovery. Reduce risks. Improve patient outcomes.
Partner with Hooke Bio and take your immunotherapy research to the next level.

This presentation highlights the development of ARGX-117, a recycling anti-C2 antibody designed to inhibit complement activation. We trace its journey from laboratory innovation to phase 2 proof-of-concept studies, showcasing its potential as a therapeutic strategy for multifocal motor neuropathy patients.

To date, over 150 drugs have been approved by the FDA for treating or preventing autoimmune and inflammatory diseases such as rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. Despite this comprehensive arsenal of therapies, there remains a significant unmet medical need for many patient groups. Elasmogen has designed a first-in-class soloMER drug conjugate tailor-made for autoimmune and inflammatory diseases. This innovative treatment utilizes a super-potent, novel-acting multivalent anti-TNFα soloMER to site-deliver an anti-inflammatory JAK inhibitor payload, Tofacitinib.

Immunocore has developed ImmTAAI, a new class of bispecific protein therapeutic designed to deliver targeted immunomodulation to treat autoimmune diseases. The effector domain comprises an agonistic anti-PD-1 VHH, which is biologically active only when target-bound and does not compete with natural ligand (PD-L1/L2), providing a wide therapeutic index. Using this targeted approach we have developed a novel bispecific molecule which specifically targets pancreatic beta cells to potentially treat type 1 diabetes.

The central role of FcRn in regulating IgG persistence and transport provides opportunities for therapy. In particular, the depletion of IgG using FcRn antagonists represents a new class of therapeutics to treat antibody-mediated autoimmunity. Recent developments related to the modulation of IgG levels, including mechanistic aspects of FcRn antagonism, will be presented.

T cell-engaging antibodies (TCEs) are bispecific adaptor proteins that connect any kind of cytotoxic T cells with target cells for redirected lysis. One arm of a TCE binds a surface antigen on the target cell, the other arm binds to the invariant CD3 epsilon subunit of the T cell receptor complex. Over the last three years, TCEs have seen an unparalleled surge in FDA approvals. A total of nine TCEs are now approved in oncology that very effectively treat as a monotherapy B cell-derived leukemia, lymphomas and multiple myeloma, and solid tumors derived from uveal melanoma and small cell lung cancer. TCEs specific for the B cell antigens CD19 and BCMA --as are approved for the treatment of leukemia, lymphomas and multiple myeloma— can also mediate deep and lasting depletion of normal and autoimmune B cells. First studies showed that this can lead to compelling remissions by TCEs in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A spade of clinical studies with B cell-depleting TCEs is under way to further explore their therapeutic potential. This presentation will focus on the development and properties of CLN-978, a novel CD19/CD3-bispecific TCE which is in clinical trials with RA and SLE patients.

Barzolvolimab is a first-in-class anti-KIT monoclonal antibody designed to inhibit activation of and deplete mast cells (MC) through an allosteric mechanism. Barzolvolimab contains Fc-modifications resulting in decreased FcyR binding and enhanced pharmacokinetics. Here we describe its discovery through Phase 2 clinical development and highlight its use in patients with MC-driven disorders.

Recent studies highlight the critical role of Fcγ receptor (FcγR)-mediated mechanisms in the efficacy and toxicity of checkpoint monoclonal antibodies (mAbs). In this talk, I will present our findings on how FcγR interactions influence mAbs' anti-tumor activity and treatment toxicity. I will also discuss our antibody-engineering strategies to optimize these mechanisms, aiming to develop safer, more effective immunotherapies.

DuoBody^®-EpCAMx4-1BB (BNT314/GEN1059) is an investigational Fc-silenced bispecific antibody (bsAb) designed to boost antitumor immune responses through EpCAM-dependent 4-1BB agonist activity. EpCAMx4-1BB bispecific enhanced T cell proliferation, activation and cytotoxic capacity of activated T cells in vitro and exhibited antitumor activity in vivo. Moreover, combining EpCAMx4-1BB with PD-1/PD-L1 axis blockade potentiated all these responses. These data provide preclinical rationale for the clinical evaluation of DuoBody-EpCAMx4-1BB.

Stellabody® is a single point mutation in the CH3 region that facilitates “on-target assembly” of immune biologics that transforms killing or agonistic potency in multiple immune protein formats i.e. mAbs, bispecific antibodies, Fc-fusions and novel scaffolds. Stellabody biologics mediate greatly (10-100x) enhanced potency in head-to-head comparisons with the equivalent standard biologic including standard-of-care mAbs in oncology on primary patient-derived clinical samples and targets in infection and immunology.

Multivalent interactions enable complex molecular recognition and signaling processes, such as the initiation of the classical complement pathway (CCP). This presentation gives an overview on how the CCP is initiated through antigen-dependent oligomerization of IgGs and subsequent recognition and activation of the multivalent zymogen C1. The presented kinetic model may serve as a basis for optimizing antibody-engineering and PK/PD modelling.

A growing number of antibodies in development are based on a complex format; however, its impact on pharmacokinetic (PK) properties remains underexplored. We systematically determined the pharmacokinetic properties of a relevant format space in vitro and in SDPK mouse studies, thereby revealing structure-PK relationships in non-specific clearance, mediated by FcRn-recycling.

Alchemab’s approach to developing therapeutic antibodies is based on the concept that the immune system is able to generate protective autoantibodies which drive unusual disease resilience. By deep sequencing the B Cell Receptor repertoires of groups of resilient individuals and looking for convergence antibody sequences shared in these individuals, we can identify those rare protective antibodies, identify the targets they bind and harness and develop them into novel therapies. This approach has been successfully applied in neurodegenerative conditions and examples will be presented.

At Monod Bio, we’ve developed the NovoBody platform, which leverages AI-assisted computational protein design to generate novel binding molecules that exploit the binding interfaces of existing antibodies (or ScFvs, or VHHs.) The process eliminates suboptimal properties of the original molecules while enhancing key functionalities without requiring extensive discovery campaigns. The result is small, single-chain, highly stable molecules that are easy to manufacture in both bacterial and mammalian cells, with customizable properties—including bispecific binding interfaces—for diverse life science applications.

The Dropzylla® Technology is a high-throughput microfluidic platform designed for the cloning of antibody repertoires. These recombinant repertoires are used to identify best-in-class antibodies targeting cancer and viral infections. MTx’ lead program, AntiBKV, is a highly effective and safe neutralizing antibody to treat BK virus infections in kidney transplant recipients. The oncology program aims to discover novel antibody-target pairs directly from tumor B cells.

We present a novel discovery platform that seamlessly combines in vivo immunisation with in vitro antibody discovery by leveraging a novel microfluidics-based semi-permeable capsule technology for recovery of natively-paired VH:VL (scFv) repertoires from millions of B cells derived from immunised animals and integrating it with our cutting-edge mammalian IgG display platform. This innovative capability enables iterative screening of original immune repertoires in final IgG format and early selection of highly developable, target-specific antibodies, thereby improving therapeutic discovery workflows.

Deep Screening is a novel high throughput method for the rapid and massive parallel screening of biologics. It enables the experimental collection of up to 10^9 scFv sequences paired with binding affinities in a 3 day experiment, identifying hits where traditional methods fail. Here we will present recent work conducted at Sortera.

PolyMap is a high-throughput method for mapping thousands of protein-protein interactions in a single tube. Here we probe antibody libraries isolated from human donors against a set of SARS-CoV-2 spike variants to demonstrate how PolyMap can be used to profile immune responses, map epitopes of hundreds of antibodies, and select functionally distinct clones for therapeutics.

ImCheck has created a set of bispecific antibodies, exploring different formats and valency to modulate anti-BTN3A agonist potency. Building on these modalities allowed to explore Vγ9Vδ2 T cell stimulation via BTN3A-mediated signal 1, immune checkpoint blocking and cis/trans anchoring to potentiate anti-tumor activity.

HVEM, a member of the TNF receptor superfamily (TNFRSF14), interacts with several molecules, including BTLA, CD160, and LIGHT. HVEM is expressed not only on hematopoietic cells but also on non-hematopoietic cells, which allows it to regulate both the priming phase of T cells in the draining lymph node and the effector phase of the T cell response at the inflamed tissue site. The engagement of HVEM with BTLA provides negative signals, while LIGHT engagement delivers bidirectional positive costimulatory signals, promoting T cell survival and effector functions.

T-cell engaging bispecific antibodies have had tremendous success in treating hematologic tumors but have shown limited efficacy in solid tumors. Alternative strategies for engaging the immune system employing safe and tunable bispecific antibodies are needed to overcome the challenges of solid tumors. In this presentation, we describe the bispecific platforms developed at Rondo Therapeutics and highlight progress on our lead program, RNDO-564, a CD28 x Nectin-4 bispecific antibody for treatment of metastatic bladder cancer.

To better harness the anti-tumor activity of T cells on top of immune checkpoint inhibition, we generated a PD-L1/CD28 bispecific antibody using our κλ-body platform to promote antitumor function through a dual mechanism of action, immune checkpoint inhibition and T cell co-stimulation. In this presentation, we provide in vitro and in vivo evidence to confirm the safety and efficient anti-tumor activity of this dual-targeting strategy.

Costimulation of tumor-infiltrating T lymphocytes by anti-4-1BB monoclonal antibodies has shown anti-tumor activity in human trials but can be associated with significant off-tumor toxicities. We designed and validated a tandem Fc-free tumor-specific 4-1BB agonist antibody fused to an engineered albumin sequence with high FcRn binding and favorable pharmacokinetics designed to confine 4-1BB costimulation to the tumor microenvironment. The antibody exhibited prolonged circulating half-life and in vivo tumor inhibition with no evidence of 4-1BB-associated toxicity when administered as purified protein or nucleoside-modified mRNA encoding the antibody.

To enable neoantigen peptides to serve as payloads in antibody-mediated targeted delivery strategies, we have developed a unique peptide tag (pTag)-scFv loading strategy that facilitates modular drug cargo loading. I will present our work on developing a novel CD40 agonistic antibody designed to bind both CD40 and the pTag-neoantigen cargo. We have explored the utility of this approach to expand CD8 and CD4 T cells in vivo and control tumor growth in lung and colorectal cancer models. Additionally, I will present unpublished data on the use of this platform for other drug modalities.

At OmniAb, we build, shape and mine custom, naturally optimized immune repertoires in divergent species to discover next generation biotherapeutics. We use high throughput phenotypic screening augmented by an AI-guided NGS workflow to navigate the vast sequence space and find high quality leads, bypassing extensive ex-vivo engineering. We demonstrate how we discovered developable anti-NKp46 binders with broad epitope coverage and affinities as building blocks for NK cell engager multispecifics.

OneChain Immunotherapeutics is developing advance CAR-T cell therapies targeting T-acute lymphoblastic leukemia (T-ALL). The use of CHO-derived scFvs support affinity tuning, epitope mapping, and benchmarking against competing candidates, while humanized scaffolds enable CAR optimization. CHO-produced anti-idiotype antibodies provide precise CAR detection and functional characterization. This integrated system bridges antibody engineering and CAR-T development, offering a scalable and rational approach to next-generation cell therapy design.

Combining single function antibodies into a bi-specific or multi specific format can present unique challenges. Stoichiometry, overall layout (IgG like, asymmetrical) and affinity can all play a key role in the success of a design with the desired activity and therapeutic developability. From multiple examples, it is clear that each bispecific development program should be treated as unique and that strategies are required to identify the optimal format. Abzena has developed a screening cascade which first places a strong focus on intelligent bispecific design which considers avidity, spacing as well as the use of different technologies. In combination with in silico analysis to identify and engineer the best partners for developability we can provide screening on a minimal number of smart designs. By leveraging unparalleled expertise in antibody production, purification, analytics and functional bioassays, we can rapidly identify and advance the most promising bispecific candidates.

Targeting novel pathways demands more than affinity. We’ll present an integrated workflow combining phage display, epitope-focused lead selection, and custom functional assays adapted for medium-throughput screening. By comparing legacy antibodies to new leads across activity, stability, and formulation-readiness, we identified candidates ready for testing in disease models. This case study illustrates how parallel optimization of function and developability streamlines antibody advancement for emerging therapeutic targets.

ADCs and TCEs are important therapeutic modalities. This presentation covers ADC & TCE antibody discovery from BsAb molecular design and antibody discovery platform selection to fit-for-purpose screening and characterization. We share our extensive experience in TCEs, highlighting key considerations for TCE optimization, such as epitope selection, affinity tuning, and PK. For ADCs, we showcase innovative early candidate screening platforms, including high-throughput internalization assays and bio-conjugation, ADC killing and stability assays.

The AlivaMab® Mouse platform, a natural mammalian display platform, outperforms in vitro technologies by leveraging in vivo immune systems to generate high-specificity, high-affinity antibodies with reduced developability and immunogenicity risks. Harnessing both natural immune mechanisms and advanced engineering, the AlivaMab platforms accelerate the transition from discovery to clinical development, with multiple candidates now in trials. Successful delivery across a range of modalities positions it as a critical tool for addressing increasingly complex therapeutic designs.

Maximizing the efficiency of PK screening assays during biotherapeutic development is advantageous when supporting multiple engineered antibody candidates and multiple programs. A microfluidic 1-hour generic PK assay using 10 µL sample and compatibility to rodent or non-human primate matrices eliminates assay development between molecules and accelerates time to results. A case study for a custom drug-specific assay for ADCs or total antibody assays will also be presented.

Explore a flexible, low-investment approach to bispecific T-cell engager discovery that enables rapid hit ID, parallel program advancement, and compressed timelines. Learn how Alloy has invested in creating optimized components and sequence-first strategies to reduce risk with a platform that has taken 12 antibodies to the clinic.

Downregulation of targets limit the efficacy of monotargeted T cell engagers (TCE). ISB 2001, a first in class TCE targeting both CD38 and BCMA, demonstrated superior tumour cytotoxicity in vitro, in vivo and ex vivo using patient samples when compared to teclistamab. Clinically, ISB 2001 demonstrated an overall response rate of 75% across all dose levels and a favourable safety and tolerability profile in heavily pretreated patients with r/r MM.

SAIL66, a next-generation tri-specific T-cell engager targeting CLDN6, CD3, and CD137, was developed using proprietary Dual-Ig® technology. Dual-Ig® enables unique ability to CD3 and CD137, but not simultaneously. SAIL66 demonstrates remarkable selectivity, avoiding cross-reactivity with related CLDN family. In vitro and in vivo studies reveal SAIL66's superior T cell activation and enhanced anti-tumor efficacy compared to conventional TCEs.

T cell-engaging (TCE) multispecific antibodies demonstrate great clinical efficacy, though their molecular complexity is a challenge for drug manufacturability, developability, and obtaining desirable PK/PD properties. Here, we showcase the discovery and engineering of novel anti-CD3 heavy chain-only antibodies (HCAbs), which demonstrate T cell cytotoxicity comparable to clinically validated TCEs when paired with IgG or TCR modalities. This work introduces a flexible new tool for enabling this important class of biologics.

Bispecifics and multispecifics that use only one light chain are a preferred format in view of manufacturability. We have established straightforward procedures to generate common light chain multispecifics from existing monospecific therapeutic antibodies, and we have also implemented an approach to obtain 2-in-1 symmetric antibodies where the light and heavy chain bind to different targets. We demonstrate that for bispecific multivalent T cell engagers the placement geometry of the binding modules is pivotal in controlling potency and mitigating cytokine release.

Our multispecific 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 Switch-DARPins that can mask the CD3-engaging moiety until a tumor target (or combination of targets) is bound. This allows for increased tumor specificity, the safer use of a potent CD3-binder with additional co-stimulatory function for enhanced efficacy, and the selection of new target combinations.

IL-2 is a potent cytokine essential for effective immune responses, but its use in cancer therapy is limited by toxicity. BON-001 was developed to overcome this by specifically targeting IL-2 to LAG3+ cells through a novel dual-binding antibody switch. In preclinical models, BON-001 effectively inhibits tumor growth, promotes expansion of tumor-specific CD8+ T cells, and shows strong combinatorial activity with anti-PD-1, supporting its potential as a therapeutic.

Plasmodium falciparum RH5 (PfRH5) is the most advanced blood-stage malaria vaccine candidate, with proven efficacy both in pre-clinical and early clinical studies and the potential to elicit strain-transcending antibody responses. From clinical trial PBMCs, we isolated and functionally characterised a large panel of anti-RH5 IgG monoclonal antibodies to better understand the features of the PfRH5 vaccine-induced antibody response. We selected a diverse subset of these mAbs to determine their efficacy against P. falciparum clinical isolates from natural infection.

By levering its platform Mabylon generates and engineers multispecific antibodies which target and neutralize exogenous allergens, providing long-term protection against allergic reactions. By deriving our variable regions from human subjects, we ensure the targeting of the most relevant allergens and epitopes. MY006, our trispecific anti-peanut antibody built from patient-derived monoclonal antibodies will start first-in-human trials by the end of 2025.

At DJS Antibodies, part of AbbVie, we aim to develop first-in-class anti-GPCR antibodies to improve patient outcomes for serious diseases. The work presented compares various antigen formats and discovery methods for isolating single B-cells following immunization with our proprietary HEPTAD technology. By utilizing a diverse range of techniques, we aim to maximize the sequence landscape obtained from our immunizations, enhancing our ability to generate effective antibody candidates.

Nanobodies are as powerful building blocks for immunotherapeutics. To facilitate nanobody discovery, we made transgenic LamaMice that expresses llama IgH molecules without association to Igκ or λ light chains. From immunized LamaMice we selected target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire. LamaMice represent a flexible and broadly applicable platform for selection of target-specific nanobodies.

In this talk, I will describe how hydrogel microparticles, combined with flow cytometry, offer a scalable platform for screening and isolating single cells based on their biological functions. This technology is unlocking new possibilities in antibody discovery by enabling direct functional characterization of antibody-secreting cells, including specificity, binding affinity, and interactions with target cells, while maintaining compatibility with existing lab infrastructure.

We have developed a powerful B cell screening platform that enables the identification of extremely rare antibody hits that possess a number of desirable features. We have successfully applied this to the discovery of antibody molecules from a range of animal species including mouse, rat, rabbit, llama, cow and human. Together with NGS expansion of the hit sequence space, we use a number of computational tools that help us go beyond the limitations of both wet-lab screening and indeed the in vivo immune response. These digital tools are helping us more efficiently identify and optimise hits with drug-like properties, accelerating their path to candidate selection and ultimately to patients.

Antibody Fragment Drug Conjugates (FDCs), a new product class tailored for solid tumours promise many advantages over ADCs including rapid tumour penetration and faster systemic clearance. However, these have been technologically-challenging to apply in oncology. Our novel approach enables high-Drug:Antibody Ratios (DARs) whilst retaining effective binding and other favourable biophysical properties. To achieve this, single-chain Fvs and other recombinant antibody formats must be considered in context with complex linker-payload chemical moieties. This platform technology has led to our lead product, ANT-045 is a cMET-targeted FDC addressing a wide range of solid tumours. ANT-045 demonstrates superior tumour cure efficacy in cMET high, moderate and low CDX and PDX gastric cancer xenograft models and better tolerability compared to the leading competitor ADCs. In a non-GLP, non-human primate study, ANT-045 was well tolerated demonstrating no signs of the usual dose-limiting adverse effects seen with ADCs (neutropenia, thrombocytopenia) with a predicted half-life in humans of around 12-14 hours supporting a viable clinical dosing strategy with a wide therapeutic window. Insights into how FDCs behave in vivo through quantitative and qualitative imaging/uptake studies and toxicological parameters will be shared and how these have informed our follow-up products.

To address the limited therapeutic window of several targeted cancer therapies we developed a chemical cleavage reaction (Click-to-Release) that allows in vivo control over drug activity. It enables controlled on-target cleavage of ADCs in the TME through a click reaction with a trigger molecule given in a second step, expanding the target scope to non-internalizing receptors. And it enables off-target deactivation of radioimmunotherapy, by selective radiolabel cleavage and clearance from circulating radioimmunotherapeutics, decreasing bone marrow toxicity. This contribution will cover examples from both ends of the therapeutic window.

The key components of Synaffix’s proprietary ADC technology GlycoConnect®, HydraSpace®, and  the toxSYN® platform enabling ADCs with best-in-class therapeutic index potential will be presented. Next, an overview on the pipeline of more than 16 GlycoConnect® ADCs that are rapidly being advanced by our partners will be provided, followed by sharing clinical development insights on the most advanced assets.

Immune-stimulating antibody conjugates (ISACs) utilize an innate immune agonist to promote lymphocyte activation in the tumor microenvironment, ultimately resulting in tumor regression and immune memory. While this technology has elicited powerful efficacy in various preclinical models, there have been a number of clinical setbacks and disappointments that have tempered the enthusiasm for this technology. We will describe the current state of the field of ISAC technology and will describe new ISAC designs that are being employed by our lab to overcome some of the reported clinical challenges. Specifically, we will focus on the role of Fc-gamma receptors in the efficacy and toxicity of ISACs.

We will present the progress of our Radio-DARPin therapeutics, designed for selective delivery of radioisotopes to tumors and surface engineered to limit uptake in healthy tissues such as kidneys. We will highlight MP0712, our DLL3-targeted candidate advancing to first-in-human trials, and our Radio-DARPin program targeting membrane-proximal MSLN. Both programs are tailored to deliver 212-Pb, a potent alpha particle-emitting isotope, and are co-developed with our partner Orano Med.

The cytosolic Fc receptor TRIM21 uses antibodies to target proteins for degradation inside the cell. This activity provides potent immune protection by destroying incoming viral particles and underpins “Trim-Away” technology. In my talk I will discuss our recent work on the molecular mechanism of cytosolic antibody-mediated degradation and the use of Trim-Away degraders to remove tau aggregates in vivo in a mouse model of Alzheimer’s Disease.

This presentation highlights efforts to develop novel transport vehicle (TV) enabled antibodies for AD that target microglia function. We’ve developed distinct transport vehicle platforms that can be differentially applied to antibodies to increase brain exposure, improve biodistribution, and enhance activity of Fab-mediated target engagement.

Tau is inextricably linked to a group of clinically diverse neurodegenerative diseases termed tauopathies. The ratio balance of the major tau splicing isoform groups (3R- and 4R-tau) is critical in maintaining healthy neurons. An imbalance causing excess 4 R tau is associated with diseases such as progressive supranuclear palsy. The work presented in this talk covers the generation of a novel 4R-tau specific “degrabody” capable of degrading 4R tau in iPSC derived neurons to probe its potential role in neurodegeneration.

Deficiencies in the hormone leptin or the leptin receptor (LEPR) causes morbid obesity in individuals with homozygous loss-of-function mutations in LEP or LEPR, and metabolic and liver disease in individuals with hypoleptinemia secondary to adipose loss. Therapies that restore leptin-LEPR signaling may resolve these metabolic sequelae. We present translational data for a fully human monoclonal antibody (mAb) that activates the human LEPR and may provide clinical benefit in disorders associated with hypoleptinemia.

The tumor microenvironment is complex, frequently immune suppressive and has become established as a critical determinant of response to antibody therapy. Understanding the tumor microenvironment in patients, including the contribution of host factors such as body composition and metabolic dysregulation on its inflammatory status, and modelling these effectively will likely be critical to advancing drug development and combination strategies. Here we will present data demonstrating that metabolic modifiers can alter the tumour immune environment in patients and then using preclinical models that this can be used in combination therapy to enhance response to immune checkpoint blockade.

The development of Inno8, an oral hemophilia drug candidate, represents a significant advancement in hemophilia A treatment. Derived from llama and alpaca VHH fragments, it underwent iterative engineering cycles, resulting in enhanced thrombin-generation potential. Animal model screenings demonstrated improved pharmacokinetic and peroral properties, including enhanced half-life based on fatty-acid protraction and oral bioavailability. Inno8's selection for clinical testing holds promise for revolutionizing hemophilia A treatment and addressing chronic diseases with an antibody-based oral drug modality.

ALL has become a model disease for novel immunotherapeutic approaches Here, we report on our studies using antibodies of either IgG1 or IgA2 isotype to mediate killing of ALL cells in vitro and in PDX models. These results suggest to investigate the clinical efficacy of IgA antibodies in combination with myeloid checkpoint blockade in ALL.

IgA has the unique properly to turn neutrophils in cancer-killing immune cells. However, just like other myeloid cells, neutrophils express SIRPa as a checkpoint inhibition molecule, that interacts with CD47 on tumorcells as ‘don’t eat me’ signal. Our present research focusses on combining the targeting on GD2 on neuroblastoma with the block of CD47 in one, bispecific IgA molecule to maximally activate neutrophils.

IgG-based therapeutics may eliminate a target via Fc-mediated effector mechanisms. However, there is a need for more potent formats. The TandemAb concept combines structural elements of IgA with that of IgG, and results in tailored designs with favorable plasma half-life and engagement of effector molecules that can eradicate tumor cells and bacteria.

Targeting tumors with γ9δ2T cells resulted in poor clinical outcomes, mainly due to the low affinity of γ9δ2TCRs for tumor antigens. We have developed affinity-enhanced γ9δ2TCRs, which led significantly improved tumor control in both in vitro and in vivo preclinical models, paving the way for next-generation γ9δ2TCR-based immunotherapies.

IgE antibodies exert pathogenic effects in allergies and protective anti-parasite immunity via high-affinity Fcε receptors on tissue-resident effector cells. We generated IgEs recognising cancer-associated antigens and translated the first-in-class agent to clinical testing. IgEs trigger pro-inflammatory effector recruitment and induction of hyperinflammatory macrophages to inhibit immunosuppression in the tumour microenvironment.

IgM is the first antibody in humoral immune response and appeared early in evolution. With high valency, IgM pentamers exhibit superior avidity, significant receptor clustering, potent effector function (CDC and ADCP) and provide opportunity for treatment of infectious disease, cancer and auto-immune disorders. Engineered IgMs have strong potential as therapeutic agents, and many biotechnical challenges of production and characterization have been resolved. Key topics and case studies will be presented.

Join fellow attendees, speakers, exhibitors and poster presenters in the exhibit hall and conference area for an evening of food, drink, poster/exhibit viewing and networking.

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

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.

Therapeutic antibody design is a complex multi-property optimization problem that traditionally relies on expensive search through sequence space. In this talk, I will introduce “Lab-in-the-loop,” a new approach to antibody design that orchestrates generative machine learning models, multi-task property predictors, active learning ranking and selection, and in vitro experimentation in a semi-autonomous, iterative optimization loop.

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, I will provide an overview of these topics and share examples to highlight their importance.

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.

BigHat Biosciences is an AI/ML-guided antibody engineering company leveraging our automated wet lab to iteratively design and optimize next-gen biotherapeutics with superior safety and efficacy. By coupling ML algorithms with experimental data, our platform continuously learns from each design cycle, analyzing key properties such as affinity, function, and developability, to guide the discovery and selection of improved antibody candidates.

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 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.

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.

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

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.

Bispecific antibodies (BsAbs) are pivotal in next-generation therapies, yet they face production challenges like secretion inefficiencies and impurity formation. GenScript's TurboCHO technology tackles these issues with an iterative workflow optimizing cell lines and media, enhancing yields. This is complemented by a tailored purification strategy using advanced chromatography to achieve high purity. Real-world case studies demonstrate its effectiveness in resolving BsAb production hurdles from development to clinical-scale manufacturing.

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.

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.

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.

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.

Dr. Barry Duplantis has a strong technical background and over a decade of experience applying drug and vaccine discovery and development platforms in commercial settings. He was the founder and CEO of a biotech startup and later led client relations at a global contract research organization. Dr. Duplantis earned his Ph.D. in Biochemistry and Microbiology from the University of Victoria, where his research focused on intracellular pathogenesis.

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.

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.

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.

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.

P. fluorescens-based Pfenex Expression Technology® transforms protein production through combinatorial screening to identify robust strains. With >20 years of development and 6 marketed products, Pfenex excels where others fail. Launched in 2024, Pfast™ offers an affordable 10 day evaluation of protein titer and quality. Tested on >30 partner proteins, Pfast significantly improved productivity challenges, improving pipeline management with seamless integration.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.