MAIN CONFERENCE DEC. 17Tuesday, 17 December 2024 - PT (Pacific Time, GMT-08:00)

emp BIOTECH has developed first-in-class Protein G solid phases that can tolerate Cleaning-In-Place (CIP) with sodium hydroxide. No loss in binding capacity was observed after 50 CIP cycles. The resins have been optimized for the purification of human monoclonal IgG. The new products are expected to be launched in Q1 of 2025.

Na+/K+–adenosine triphosphatase (NKA) is a transmembrane protein consisting of three subunits: a, b, g. A progressive decline of NKA activity exacerbates neurodegeneration in the aging process. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (897DVEDSYGQQWTYEQR911) of the NKAa1 subunit. It was demonstrated that DR5-12D produced therapeutic effects against neurodegenerative diseases. Therefore, DR5-12D may represent a new therapeutic strategy for neurodegenerative diseases.

Growth differentiation factor 15 (GDF-15) is a stress induced cytokine that causes anorexia and weight loss, and higher circulating levels are associated with cachexia and reduced survival in patients with cancer. Inhibition of GDF-15/GFRAL biological activity reverses cachexia in numerous preclinical tumor models, and ponsegromab (a novel, first in class humanized monoclonal anti-GDF15 antibody) is being developed as a therapeutic agent for cancer cachexia.

This talk describes the regulation of energy balance and appetite beyond traditional hormonal mechanisms. We discuss Peptide Predictor, a computational tool that identified BRINP2-Related Peptide (BRP), an anorexigenic peptide cleaved by PCSK1. BRP significantly reduces food intake and obesity through a unique central signaling pathway, without affecting other metabolic behaviors. This discovery highlights the potential of peptide prediction platforms in uncovering new metabolic regulatory mechanisms and biological pathways.

We show AAV delivery of full-length antibodies targeting GA-dipeptide proteins in C9orf72 ALS/FTD BAC-transgenic mice reduces repeat associated non-AUG (RAN) protein levels, improves behavior and neuropathology, and increases survival. AAV delivery of high-affinity antibodies is a novel strategy to achieve broad and sustained CNS expression and biodistribution of therapeutic antibodies. These data open new possibilities for developing AAV-antibody therapies as a novel approach for C9orf72 ALS/FTD and other neurodegenerative disorders.

The inability of antibodies to penetrate the blood-brain barrier is a key limitation to their use in diverse applications. We are developing bispecific antibodies that engage either CD98hc or transferrin receptor, which results in the transport of IgGs and other biologics into the CNS. We will highlight our findings related to the unique advantages of CD98hc and transferrin receptor bispecific antibodies, especially related to the impact of target engagement in the CNS on pharmacokinetics and CNS distribution. Finally, we will discuss our recent findings on applications of bispecific antibodies for targeted CNS drug delivery.

Alector is a leader in the field of Neuroimmunology - harnessing the brain's immune system to cure neurogenerative disorders. Here we describe our Neuroimmunology pipeline and our novel Blood-brain barrier crossing technology (ABC) designed to further enhance brain delivery of antibody and protein therapeutics to address neurodegenerative diseases.

Immunogenicity risk assessment is an essential step in bringing therapeutic drugs to the market. ProImmune's risk management tools evaluate immunogenic epitopes and the corresponding functional T cell responses that can lead to unwanted immune responses. Case studies will highlight how the integrated platform is used to address key questions in the drug development phase.

Using the Pfenex Expression Technology®, we achieved 15g/L of a modified VHH molecule engineered for site-specific ADC conjugation. The innovative Pfenex platform, based on P. fluorescens, produces various antibody formats including Fab's and novel Picobodies™. The platform effectively utilizes multiple genetic elements, host strains, and automated workflows to optimize protein expression from early research through full commercialization, with six approved products to date.

Developed by a core group of AbTherx scientists and acquired by Gilead Sciences in 2023, Atlas™ Mice are a suite of transgenic mouse technologies for human antibody discovery. AbTherx has worldwide rights to this novel platform, successfully developing technologies that express the full diversity of human antibody HC and k-LC repertoires, enable the development of bispecific antibodies through a novel binary fixed light chain, and use natural mechanisms to generate long CDRH3 antibodies to address challenging drug targets.

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.

Introducing a novel FACS-based strategy paired with our AbTheneum platform, this presentation showcases a workflow to deliver higher yield of hits from a discovery campaign. By combining high-precision cell isolation with a robust engine for parallel screening and sequencing of all IgGs, we reveal how this synergy boosts hit rates and diversity, even in challenging low-titer conditions across various campaigns.

Asymmetric bispecific antibodies have a great potential for becoming the next big leap for antibodies, but present challenges for purification. One way to purify these molecules is by using avidity effects on affinity protein A and protein L resins. In this presentation, we show newly developed tools and a systematic approach that can be used to achieve high purity of the correctly paired antibody in the capture step.

Quickly obtaining qualified clones from multiple antibody generation technologies is crucial for advancing functional antibodies that eventually constitute the therapeutics of tomorrow.

Explore how Heavy Chain Only Antibodies (HCAb) function as versatile building blocks for bispecifics. Understand the potential of fully human HCAbs derived from Harbour Mice® in developing bispecifics with outstanding druggability. Delve into the next-generation HBICE® bispecific platform for immune cell engagement. Discover emerging technology platforms on the horizon. Examine an engaging case study of HBICE® from concept to IND.

Oxidative stress occurs in many autoimmune diseases which give rise to oxidative post translationally modified (oxPTM) neoepitopes that are recognized by the immune system as ‘non-self’. The detection of autoantibodies against oxPTM neoepitopes, might improve early diagnosis and monitoring of disease activity. Importantly, oxPTM neoepitopes accumulating in the diseased tissue can be exploited for targeting therapeutic specifically to diseased tissue. Studies on musculoskeletal diseases and type 1 diabetes will be reviewed.

Mast cells (MCs) are key players in many allergic and inflammatory diseases. Briquilimab is a monoclonal antibody that binds to c-Kit, blocking stem cell factor from binding and activating c-Kit, leading to MC apoptosis and depletion. Pharmacokinetic and pharmacodynamic evaluation of briquilimab in non-human primates and in murine disease models of asthma and dermatitis suggest that briquilimab-mediated depletion of MCs is well-tolerated, protects against MC activation from various stimuli, and significantly reduces tissue inflammation.

Obexelimab is a CD19 x FcgRIIb bifunctional monoclonal antibody resulting in an inhibitory effect, rather than depletion, across B cell lineage (pro-B cells, pre-B cells, B cells, plasmablasts and CD19-expressing plasma cells). It mimics natural antigen-antibody complex for inhibition of B cells. It is being developed for multiple I&I indications for autoimmune diseases. Clinical data from obexelimab-treated patients and relevant mechanisms of action will be discussed.

InduPro leverages inherent and induced proximity of cell surface proteins to discover novel biology and enable therapeutic development. We demonstrate that re- location of immunomodulatory proteins into or out of the immune synapse using select bi-specific antibodies can alter T cell activation. Application of this approach to dampen T cell signaling for the treatment of autoimmune disease will be presented.

DNTH103 is an investigational, fully human, half-life extended, potent monoclonal antibody engineered to selectively target the classical pathway by inhibiting only the active form of the C1s protein, to enable a more convenient subcutaneous, self-administered injection dosed as infrequently as once every two weeks. Additionally, selective inhibition of the classical complement pathway may lower patient risk of infection from encapsulated bacteria by preserving immune activity of the lectin and alternative pathways. DNTH103 is in development for Myasthenia Gravis, CIDP and MMN.

Regulatory T cells (Tregs) are naturally occurring immune cells that modulate immune responses and promote tissue homeostasis. Treg dysfunction is characteristic of many chronic autoimmune and inflammatory diseases. Sonoma Biotherapeutics genetically engineers and expands patients’ Tregs as a “living therapy” with antigen receptors that target diseased tissue to regulate inappropriate immune responses, reducing inflammation and facilitating tissue repair without compromising host defense.