A Pioneering Platform for Precision Therapies
Hummingbird Bioscience’s Rational Antibody Discovery platform leverages data-rich, systems biology approaches to identify critical functional regions of a target protein, drive production of antibodies against these epitopes, and then isolate the antibodies that bind to them, thereby optimizing the therapeutic potential of a target.
This systematic and rational approach overcomes many of the common challenges such as tolerance and epitope instability, and allows us to efficiently and precisely engineer next-generation precision therapies that uniquely hit the right targets for the right patients.
Rational Antibody Discovery Platform
mAbHits AbvantageTM
uses an immunoengineering system to manipulate an immune response to control the production of antibodies against defined optimal yet elusive epitopes on a disease associated protein. mAbHits increases the proportion of usable therapeutic antibodies.
mAbPredictAI
uses AI-powered computational biology to integrate and analyze data from multidisciplinary sources to produce validated insights into the biology of the disease and provide predictions regarding which epitopes on a disease associated protein will yield antibodies with optimal efficacy and safety profiles.
Classical Approaches vs. Rational Antibody Discovery
Missing the Mark
Classical approaches to antibody discovery often led to the majority of antibodies produced missing the optimal epitopes.
Hitting the Spot
Our Rational Antibody Discovery platform systematically identifies optimal target epitopes, and immunoengineers an immune response that results in majority of the resulting antibodies hitting the desired epitopes.
Applications of our Platform
Design of Antibodies for ADCs
The platform enables specific, epitope-directed discovery for optimal functionality (specificity, affinity, internalization) and developability. These capabilities enable us to build ADCs that have an optimal safety-efficacy profile.
Additionally, we also engineer the antibody Fc to abrogate off-target FcγR-mediated uptake and optimize ADC exposure profile.
Design of Functional Antibodies
The challenges in discovering functional antibodies are two-fold: knowing where antibodies must bind on a disease-related protein to provide therapeutic benefit and isolating antibodies that bind these optimal and often elusive epitopes. Our platform integrates computational biology and a mechanistic understanding of disease to gain insights on protein structure and function relationships, predict ways to manipulate the system through antibody binding, and then immunoengineers an antibody response against these epitopes.
Drugging Multipass Transmembrane Proteins
Multipass transmembrane proteins, such as G protein-coupled receptors (GPCRs) and ion channels, are difficult to drug because the cell membrane contains many competing immunogenic epitopes, but if removed from the membrane, the protein becomes distorted from its natural shape. Our platform overcomes this issue of competition by immunoengineering an antibody response towards optimal epitopes on the multipass protein when it is in the membrane.
Agonist Antibodies
Most antibody drugs disrupt protein function. “Agonism” is the opposite, i.e. when an antibody activates a protein’s function for a therapeutic benefit. This can be a highly desirable attribute for a drug, for example, when we want to activate the patient’s own immune system to attack the tumor, however, to achieve agonism the antibody must bind to a very specific region of the target protein. Our platform immunoengineers an antibody response towards these specific epitopes to achieve potent activation; specific protein binding enables the circumvention of autoimmune responses against healthy cells that presents similar surface proteins.
Overcoming Immunodominance
Immunodominance occurs when certain epitopes of a target protein are more likely than others to generate an immune response, resulting in almost all antibodies binding to those dominant epitopes. However, the elusive epitopes that do not yield antibodies are often optimal for correcting disease mechanisms. Immunodominance is a common reason classical approaches can fail to generate effective functional antibodies, and an important challenge that our platform overcomes by immunoengineering an antibody response towards these elusive epitopes.
Overcoming Tolerance
Tolerance is the immune system’s failure to recognize and raise antibodies to a foreign protein because the protein is too similar to the host’s own proteins. Classical approaches to overcoming tolerance are often time- and resource-intensive as they involve changing the host itself. Our platform overcomes this by immunoengineering an immune response to these conserved epitopes no matter the host.
Stable Regions of Viral Targets
Rapid mutation of viral proteins allows viruses to evolve and evade the immune system and also makes it challenging to develop successful antiviral therapies, including antibodies. Our platform tackles this by predicting epitopes on key viral proteins that are unlikely to mutate and then immunoengineers an immune response to those conserved epitopes.
