MAIN CONFERENCE DEC. 18 - PT (Pacific Time, GMT-08:00)
- Takashi Sato, PhD - Chief Scientist & Technical Architect, Life Science Product Division, Rigaku Corporation
The design and implementation of phage display antibody libraries for discovery and optimization of antibodies, called ALTHEA Libraries, will be presented. The potentail of these antibody discovery platforms will be illustrated with two case studies: (1) isolation and optimization of broadly anti-SARS-CoV-2 neutralizing antibodies and (2) generation and characterization of a panel of anti-PD-1 antibodies with diverse binding and functional profiles.
- Juan Carlos Almagro, PhD - Founder and CEO, GlobalBio, Inc.
- Paul Parren, PhD - Founder and CSO, Gyes BV
- Andrew Bradbury, MD, PhD - Chief Scientific Officer, Specifica
It is relatively straightforward to select antibodies or VHHs that bind targets, but much more challenging to generate antibodies with functional activity. Here we describe the use of TripleBar’s microfluidics system to select functional CD3 activating antibodies from Specifica’s Generation 3 library platform.
- Sarah Ives - Vice President, Biopharma, Triplebar Bio
- Andrew Bradbury, MD, PhD - Chief Scientific Officer, Specifica
Discovery of biotherapeutics against challenging targets such as integral membrane proteins, membrane protein complexes, and heavily glycosylated surface proteins using display technologies remains a challenge. We have utilized therapeutic-ready phage- and yeast-display platforms expressing a diversity of formats to pan against both cells and virus-like particles. Using these novel reagents and protocols, we have managed to discover biotherapeutics to traditionally display "unfriendly" targets.
- Jeff Barker, Ph.D. - Principal Research Scientist I, AbbVie Bioresearch Center
We have developed a droplet-microfluidic single-cell-based platform for the repertoire biobanking and expression of the antibodies of up to one million human B cells in HEK cells. This cognate biobank represents 80% of the input cells, the robustness of this format enables any screening process including droplet microfluidic sorting.
This technology is applied for the direct discovery of tumor-reactive antibodies from tumor-infiltrating B cells in cell-based assays.
- Christoph Esslinger, Ph.D. - CSO, Memo Therapeutics
- Sally Ward, PhD - Professor and Director, University of Southampton
- Karen Silence, PhD - Head Preclinical Product Development, Argenx
Groundbreaking immunotherapies known as immune checkpoint inhibitors mobilize the immune system against cancer by blocking the protein interactions that suppress immune cell activation. However, limited response rates to these therapies necessitate the development of new molecules that act through alternative mechanisms. Here, we describe the discovery and design of multispecific antibody fusion proteins incorporating single-domain shark antibodies that improve upon clinical drugs, presenting a novel modality to advance cancer treatment.
- Jamie Spangler, PhD - Associate Professor, Johns Hopkins University
A subset of cow antibodies have a heavy chain “ultralong” CDR3 region that can be over 70 amino acids in length, with a disulfide-bonded “knob” domain that protrudes far from the antibody surface. These knob domains can be produced independently of the antibody to generate tiny, high affinity, binding fragments. The novel genetics, structural biology, and biomedical applications of ultralong CDR3 antibodies will be discussed.
- Vaughn Smider, MD, PhD - Adjunct Professor, Molecular Medicine, The Scripps Research Institute
Ion channels are an important target class which are under-served by biologics. Maxion have shown that small cys rich peptides with ion-channel modulating activity can be inserted into antibody CDRs while retaining their function. The resulting 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 to therapeutically relevant ion channel targets.
- Aneesh Karatt Vellatt, PhD - Chief Scientific Officer, Maxion Therapeutics
Abalone Bio’s Functional Antibody Selection Technology (FAST) platform combines biology and machine learning (ML) to identify and design functionally active antibody drugs. FAST simultaneously tests the entire diversity of antibody libraries directly for the desired function and produces library-scale sequence-function datasets that uniquely power generative protein language models to design novel active antibody sequences. FAST-discovered antibodies have been demonstrated to have agonist activity in vitro and in vivo.
- Monica Schwartz, Ph.D. - Vice President of Antibody Discovery, Abalone Bio
Characterizing the binding parameters (ka, kd, KD) of antibody:receptor interactions is crucial in drug discovery. However complex Abs and/or receptors are not always amenable to traditional biophysical methods (i.e., SPR, BLI, etc.), necessitating cell-based binding assays. We developed a pre-equilibrium assay to simultaneously determine the binding kinetics of up to 30 therapeutic Abs on living cells.
- Eric Janezic, Ph.D. - Principal Scientist, Genentech
Protillion combines ML-guided antibody design technology with purpose-built chip-based high-throughput instrumentation to tackle challenging problems in therapeutic protein engineering. The platform is capable of characterizing the binding affinity of up to 10^6 antibody variants in a 2-day automated run. This unique approach enables identification of better antibody candidates that meet challenging product profiles, including pH-dependent binding, cross-species reactivity, and stringent developability.
- Curtis Layton, PhD - CEO and Co-Founder, Protillion Biosciences
The pathogenicity of autoreactive antibodies has been demonstrated for many autoimmune diseases and the isotype/subclass profile can potentially influence the disease pathophysiology. Although often overlooked, IgA autoantibodies are increasingly recognized in different autoimmune indications. Here, we describe the development of anti-IgA monoclonal antibodies that can actively remove IgA from the circulation and block binding of IgA to its main Fc receptor FcαRI. Given the abundancy of IgA in human serum (1-3 mg/mL), both Fab and Fc engineering were optimized to design a monoclonal antibody with the desired properties.
- Sofie Voet, Ph.D. - Principal Scientist, Argenx
Inhibitory checkpoint receptor (IR) agonists have the potential to restore immune homeostasis for patients with autoimmunity but are limited by their ability to non-discriminately bind activating FcγRs. IR agonists anchored to FcγRIIb, the inhibitory Fc receptor, have the potential to provide superior agonism by avoiding inflammatory cytokine responses and limiting APC activation. Discovery and development of a Dual-cell Bidirectional PD-1 FcγRIIb agonist antibody that activates multiple inhibitory pathways in more than one cell type to regulate both sides of the immune cell synapse will be discussed.
- Jyothsna Visweswaraiah, PhD - Director, Biotherapeutics Drug Creation, Seismic Therapeutic
Although antibodies are actively explored as therapeutic for bacterial infections, their narrow specificity poses a challenge due to the broad diversity between bacterial species. We reveal that conversion of highly specific anti-staphylococcal IgGs into IgM induced cross-reactivity with a range of bacterial species.
- Remy Muts - PhD Candidate, UMC Utrecht
- Brett Averso - Chief Technology Officer, EVQLV
Wheeler Bio’s Portable CMC® open-source upstream and downstream platform processes generates a predictable, reliable, and scalable approach for accelerating the movement of molecules from discovery, through lead candidate selection, and into clinical manufacturing. The Portable CMC® platform and hybrid-mechanistic process model was developed using data from both stable bulk cultures (SBCs, also known as bulk pools) and derivative clones to enable well-controlled cell lines, high titers, process robustness, scalability, and speed-to-clinic
- Aaron Pilling, PhD - Director, Business Development, Wheeler Bio
- Xin Yuan, PhD - Senior Scientist, DPBio
Each immune complex is unique and affects its own set of Fc functions. To treat the antibody as a sum of two independent domains, the Fab and Fc, is fraught with false assumptions that could negatively impact therapeutic development. SeromYx’s high-throughput GCLP platform enables the empirical and comprehensive determination of the antigen-specific Fc functional profile of therapeutic antibodies uncovering vital insights into their safety and immune mechanisms of efficacy upfront.
- Shashi Jatiani, PhD - Director of Research, SeromYx Systems
At Lightcast we are developing a next-generation technology platform that enables the direct, precise interrogation of single cell heterogeneity, interactions and functional dynamics at scale. Across a broad range of disciplines from basic and translational research to drug discovery, we provide the freedom to accelerate discovery and apply novel biological insights. This session will provide an overview of the technology and explore the potentially powerful impact in understanding and applying single cell functional understanding in some key areas of cancer therapeutics.
- Ali Glaser - Market Development Specialist, Lightcast
- Laura Walker, PhD - Head of Infectious Disease Biotherapeutics Discovery, Moderna
- Mitchell Ho, PhD - Senior Investigator, Laboratory of Molecular Biology, NIH NCI
Current approaches to mine functional immune responses are generally limited in quality or throughput. To address these limitations, our group established high-throughput functional screening platforms for natively paired antibodies and T cell receptors generated in vivo. Here we will share several case studies of immune mining and engineering from in vivo leads.
- Brandon DeKosky, Ph.D. - Assistant Professor of Chemical Engineering, MIT
Primary mouse B cells were engineered so their heavy and kappa variable-chain loci were scarlessly overwritten by their respective human antibody variable-chain genes. These B cells proliferated in vivo to generate potent neutralizing plasma, and affinity matured to develop broader, more potent, and more bioavailable HIV-1 and SARS-CoV-2 neutralizing antibodies. This approach improves the clinical utility of antibodies and biologics, enables more human-like vaccine models, and suggests new cell-based therapies.
- Yiming Yin, Ph.D. - Postdoctoral Research Fellow, Boston Children's Hospital
- Jamie Orengo, Ph.D. - Vice President Research, Allergy and Immunity, Regeneron
- Thomas Pillow, PhD - Distinguished Scientist, Genentech
- Gregory Adams, PhD - Chief Scientific Officer, Elucida Oncology
MYTX-011 is an investigational, pH-sensitive, vcMMAE ADC. It has been designed to benefit a broader population of patients whose tumors express lower/moderate levels of cMET. MYTX-011 drives increased internalization and cytotoxicity and shows robust activity in xenograft models across a range of levels of cMET expression. Early clinical data demonstrate a differentiated profile: extended PK, low free MMAE release, and low incidence of side effects commonly associated with vcMMAE ADCs.
- Brian Fiske, Ph.D. - Chief Scientific Officer, Mythic Therapeutics
Chain exchange technologies can be used to generate binder-format matrices of bispecific antibodies. Similar to the optimization of bsAbs, chain-exchange can also generate ADC-matrices by combining different binders, formats, attachment-positions and payloads. As an example, a Her2-ADC matrix with payloads attached in different formats, positions and stoichiometries reveals that ‘format-defines-function’ applies not only to bsAbs but also to ADCs.
- Ulrich Brinkmann - Expert Scientist, Large Molecule Research, Roche Innovation Center Munich
Payload resistance is a critical concern for ADCs. Combinations may be beneficial but therapeutic windows are limited. Hummingbird Bioscience's dual-payload ADC platform is a targeted, single-agent approach designed to overcome resistance and maximize therapeutic window. HMBD-802, an anti-HER2 dual-payload ADC shows robust efficacy in trastuzumab deruxtecan resistant models and good tolerability.
- Jerome Boyd-Kirkup, PhD - Chief Scientific Officer and Co-Founder, Hummingbird Bioscience
The rapid evolution of SARS-CoV-2 has resulted in continuous escape from traditional IgG-based monoclonal antibody (mAb) therapeutics, suggesting that new antibody engineering and delivery strategies are required to keep pace with viral evolution. In this presentation, I will describe the discovery and engineering of multi-specific antibodies with broad and potent activity against SARS-CoV-2 variants and the in vivo delivery of these constructs using mRNA technology.
- Anna Wec, PhD - Associate Director, Infectious Disease Research, Immunology, Moderna
Identifying novel epitopes naturally targeted by the human antibody repertoire is an important component of immunogen design aimed at eliciting protective antibodies to infectious disease. I will describe techniques used to survey and characterize monoclonal antibodies generated in response to experimental vaccines in human clinical trials.
- Sarah Andrews, Ph.D. - Chief, B Cell Immunobiology Section, Vaccine Research Center, NIH
After vaccination, responding B cells may differentiate along the extrafollicular path, which leads to the production of short-lived plasmablasts, or along the germinal center (GC) route, which leads to the generation of long-lived plasma cells and memory B cells. GCs are the primary site of affinity maturation, the process whereby the binding affinity of induced antibodies to vaccine antigens increases with time after vaccination. We have recently shown that mRNA vaccination against SARS-CoV-2 in humans can elicit a GC reaction that engages pre-existing memory B cell clones and de novo ones that can target new epitopes, broadening the spectrum of vaccine-induced protective antibodies. These findings raised the following important questions: (1) What are the dynamics of vaccine-induced GC B cell responses in humans? (2) Do responding GC B cells accumulate somatic hypermutations (SHM) after mRNA vaccination? (3) Can a GC reaction be remounted upon repeat mRNA vaccination? These are some of the questions I will discuss in my presentation.
- Ali Ellebedy, Ph.D. - Leo Loeb Endowed Professor, Pathology & Immunology, Washington University School of Medicine
99% of a dose of an ADC is eliminated by normal tissues, causing efficacy limiting toxicities. Shasqi has developed an approach to overcome this problem by separating tumor binding from the payload and enabling selective payload activation at the tumor using click chemistry. This approach maximizes efficacy and therapeutic index by reducing toxicities.
- Travis Biechele, PhD - VP and Head of Research, Shasqi
Radiolabeled antibodies are essential in cancer theranostics and radio-immunotherapy (RIT) due to their high specificity for cancer antigens. While promising, RIT faces challenges including long half-life leading to prolonged radioactivity exposure. This presentation explores strategies to improve RIT efficacy and safety, including combination therapies with drugs that modulate radiation response or interact with the immune system, as well as antibody modifications, and optimized administration techniques.
- Marika Nestor, PhD - Professor in Biomedical Radiation Sciences, Uppsala University
Immunostimulatory antibody conjugates (ISACs) often rely on Fcγ receptor (FcγR) interactions to activate immune cells and drive tumor regression. However, these interactions may also contribute to immune-related side effects. To address this, we are developing deglycosylated ISACs that bypass FcγR binding. Tested in HER2+ breast and Trop2+ pancreatic cancer models, these ISACs maintained potent tumor-specific immune activation while potentially minimizing off-target effects. Ongoing studies are exploring the link between immunogenicity and FcγR binding.
- Anqi Zhang, PhD - Postdoctoral Fellow, Binghamton University