Cambridge Healthtech Instituteの第11回年次
Antibodies Against Membrane Protein Targets - Part 2
PLENARY KEYNOTE PROGRAM
Plenary Keynote Introduction (Sponsorship Opportunity Available)10:45 am
PLENARY: The New Science of Therapeutics
Jay E. Bradner, MD, Physician Scientist, Former President, Novartis Institutes for BioMedical Research, Inc.
I will share reflections on how new paradigms in the science of therapeutics are creating opportunities to approach historic challenges in medicine. Specifically, I will share approaches to targeting transcription factors and discuss how modularity is a paradigm for next-generation low-molecular weight and biological therapeutics. Finally, I will offer reflections on drug development and the fitness, opportunities, and challenges of the biomedical ecosystem.
PLENARY: Accelerating Drug Discovery Using Machine Learning and Cell Painting Images
Microscopy images can reveal whether a cell is diseased, is responding to a drug treatment, or whether a pathway has been disrupted by a genetic mutation. In a strategy called image-based profiling, often using the Cell Painting assay, we extract hundreds of features of cells from images. Just like transcriptional profiling, the similarities and differences in the patterns of extracted features reveal connections among diseases, drugs, and genes.
Enjoy Lunch on Your Own12:25 pm
Welcome Remarks1:45 pm
ENGINEERING AND DEVELOPMENT STRATEGIES FOR GPCR AND ION CHANNEL TARGETS
Strategy for Targeting Class A GPCRs Based on Structural Insights
Dawei Sun, PhD, Scientist, Structural Biology, Genentech
G protein-coupled receptors (GPCRs) are the largest class of cell surface drug targets which play central roles in regulating many cellular and physiological processes. We present structures of a family A GPCR in both the inactive, antibody-bound, and the active, ligand-bound state. Our structures elucidate a novel ligand-mediated activation mechanism and shed light on the molecular mechanisms of GPCR-ligand recognition and antibody-mediated inhibition, potentially facilitating therapeutic intervention on this target.
Novel Multi-Specific Biomolecules to Modulate Membrane Proteins
Xin Zhou, PhD, Assistant Professor, Biological Chemistry & Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School
Targeted protein degradation is an emerging concept for regulating challenging membrane drug targets. Unlike traditional antibody approaches, targeted degradation methods do not rely on neutralizing binders. This presentation introduces a new protein degradation technology based on multi-specific antibodies. This novel molecular archetype is highly effective in degrading various types of membrane proteins, including single-pass, multi-pass, native, or synthetic receptors, with a degradation efficiency of over 90% in various cellular systems.
Volker Lang, PhD, Managing Director, AbCheck s.r.o.
AbCheck has developed a number of technologies for efficiently discovering high-quality MAbs for next-generation protein therapeutics. Our drug discovery platform offers modular solutions to overcome target-specific challenges and improve success rates for drug discovery campaigns. Our proprietary microfluidics approach enables direct one-step sorting for function and/or other critical criteria with high throughput of millions of droplets per day for the discovery of antibodies to both known and emerging functional targets.
Refreshment Break in the Exhibit Hall with Poster Viewing3:25 pm
Insights from Current Pipelines of Antibody-Based Therapeutics against GPCR, Ion Channel, and Transporter Targets
Catherine Hutchings, PhD, Independent Consultant
Multi-pass transmembrane proteins represent some of the most important drug target classes across a wide range of therapeutic areas. An update on antibody-based therapeutics in the GPCR, ion channel, and transporter R&D pipeline will be provided outlining the breadth and diversity of the target landscape.
Anti-GPCR Antibody Discovery for Inflammatory and Fibrotic Disease
Joseph Illingworth, PhD, CSO, DJS Antibodies
DJS Antibodies is a biotech company focused on discovery of antibodies to GPCRs, aiming to develop treatments for inflammatory and fibrotic diseases. In October 2022, we joined AbbVie, Inc., where we are expanding on this core mission while acting as AbbVie’s first UK research site. In this talk we will share our experiences discovering and developing the first monoclonal antibody inhibitor of LPAR1, a clinically-validated target for fibrotic disease.
Dinner Short Course Registration*5:00 pm
*Premium Pricing or separate registration required. See Short Courses page for details.
Enabling the Discovery of Therapeutic Antibodies Targeting Challenging Membrane Proteins
Mauro Mileni, PhD, Founder & CEO, Abilita Bio
Discovering therapeutic antibodies against multi-span membrane proteins, such as GPCRs and ion channels, remains a formidable challenge primarily due to poor antigen quality. The EMP technology can remove roadblocks for the most challenging targets, by enabling use of the whole target protein with properly folded transmembrane domains to be employed in discovery campaigns. Case studies will be shown where antibody hits with high affinity, selectivity, and developability were identified.
Close of Day8:00 pm
Registration and Morning Coffee7:30 am
Discovery and Development Story of AD-214, an Fc-Fusion Protein i-Body for Fibrosis
Michael Foley, PhD, CSO, AdAlta
i-bodies are small, stable, human scaffolds inspired by the shark single domain antibodies. AD-214 is an i-body with affinity for CXCR4, a GPCR which is known to be upregulated in one cancer and several fibrotic conditions. AD-214 has anti-fibrotic activity in several preclinical models of fibrosis and has been found to be safe in a first in human clinical trial. The i-body platform has potential in several other disease modalities.
Discovery of High-Affinity Functional Antibodies Specific for CXCR5 and Other Multi-Pass Membrane Proteins
Ernest Smith, PhD, Senior Vice President, Research; CSO, Antibody Discovery, Vaccinex
We have developed a fusion protein technology to enable the direct incorporation of multi-pass membrane proteins into the membrane of two antigenically distinct poxviruses. The protein of interest is correctly folded and expressed in the cell-derived viral membrane and does not require any detergents or refolding before downstream use. Antigen expressing virus can be readily purified and used for antibody selection using any in vitro display platform or for immunization and ex vivo antibody discovery. We will describe the use of this technology to discovery high-affinity functional antibodies specific for CXCR5 and other multi-pass membrane proteins.
Artificial Intelligence-Based de novo Design of Antibodies against GPCR and Ion Channel Targets
Murat Tunaboylu, PhD, Co-Founder and CEO, Antiverse
At Antiverse, we have developed an Artificial Intelligence (AI)-powered de novo antibody discovery platform, which designs antibody candidates against difficult-to-drug targets, including GPCRs and ion channels. Computational methods offer strong advantages over traditional antibody discovery methods. Through a combination of machine learning to design target-specific antibody libraries and hyper-expressing cell lines expressing abundant epitope, we facilitate the generation of diverse antibody candidates, with enhanced affinity, specificity, and improved therapeutic potential.
Agonist Biologics to MC1R: A New Way to Address Autoimmune and Related Conditions
Thomas Fontaine, Senior Researcher, Confo Therapeutics
Recent studies have suggested a potential link between MC1R and autoimmune diseases. However, the lack of selective tools has slowed down the development of new drugs. We will discuss how we have identified very selective, high-potent MC1R agonist biologics using Confo’s proprietary technology to lock GPCRs in the active state, and how these exhibit anti-inflammatory activity in a preclinical in vivo model.
In-Person Group Discussions10:05 am
Coffee Break in the Exhibit Hall with Poster Viewing10:50 am
Novel Antigen Formats for Improved Ab Discovery against Challenging Integral Membrane Proteins
Rajesh Sundaresan, PhD, Scientific Leader and GSK Fellow, Protein Cell and Structural Sciences, GlaxoSmithKline
Delivering antigens/immunogens for biologics discovery against challenging membrane targets is often a bottleneck in the discovery process. At GSK we have successfully employed both novel genetic and biochemical approaches, through an enabling platform, to deliver membrane proteins for Ab discovery programs. I would like to present our success stories and key learnings from this exercise, highlighting the improvement in cycle times, thereby allowing early start to screening campaigns.
KEYNOTE PRESENTATION: Multiplexed Validation and Detection of Anti-GPCR Antibodies
Thomas P. Sakmar, MD, Professor, Chemical Biology, Rockefeller University
We developed a multiplexed immunoassay to test >400 anti-GPCR Abs from the Human Protein Atlas targeting a library of 215 expressed GPCRs representing all GPCR subfamilies. We found that ~61% of Abs tested were selective for their intended target, ~11% bound off-target and ~28% did not bind to any GPCR. These results provide insights into the immunogenicity of GPCR epitopes and form a basis for designing therapeutic Abs and for detecting pathological auto-anti-GPCR Abs.
Sponsored Presentation (Opportunity Available)12:30 pm
Transition to Lunch1:00 pm
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own1:05 pm
Dessert Break in the Exhibit Hall with Last Chance for Poster Viewing1:35 pm
Discovery and Optimization of Novel GPCR Biologics for CV/Renal Disease
Peter McNamara, PhD, CSO, Tectonic Therapeutic
Complex cellular targets such as G protein-coupled receptors (GPCRs) and other multi-transmembrane proteins represent a significant challenge for therapeutic antibody discovery, primarily because of poor stability of the target protein upon extraction from cell membranes. I will present the strategy we used to discover a GPCR biologic with optimized potency, PK, and biophysical characteristics and will also discuss the criticality of antigen design strategy to connect affinity maturation to potency improvements.
TARGETING TRANSPORTERS AND ION CHANNELS
Case Studies of Ion Channel Antibody Discovery Programs
Trevor Wattam, PhD, Scientific Leader, Antibody Discovery, GlaxoSmithKline
Complex membrane targets still present many challenges for antibody discovery platforms. Using new methods and updated methods in antigen preparation, immunization and screening can increase the probability of success for generating and isolating these rare antibodies to the challenging targets.
Rapid Generation of Conformation-Specific Antibodies Using the Linkster Discovery Platform
Roger Dawson, PhD, CEO, Linkster Therapeutics AG
Antibody drug campaigns against challenging targets often lead to non-developable antibodies. Failures are associated with (i) the high biological target complexity of ion channels, GPCRs, and SLC transporters, (ii) low library quality, and (iii) display and screening technologies unfit for non-controlled conditions. Here, case studies of highly stable and conformation-specific antibodies are presented using the smart library design and novel technology of Linkster discovery platform.
Therapeutic Antibody against MCT1 Transporter
Jay Rothstein, PhD, CSO, ImmuNext
Monocarboxylate transporter 1 (MCT1) is a membrane protein that transports lactate and is required for effector functions of activated immune cells. Blocking lactate transport has a potential therapeutic benefit for treating a wide number of autoimmune diseases. To address this unmet need we developed an anti-human MCT1 mAb that blocks solute transport (lactate efflux) from activated lymphocytes. This first-in-class inhibitor represents a new class of drugs to treat autoimmune diseases.
Close of Conference4:20 pm