At Hummingbird, we believe that our unique, multidisciplinary approach that combines systems biology with data science can overcome the challenges of classical methods of therapeutics discovery, and fundamentally transform the delivery of truly personalized medicines.
We integrate cutting-edge innovations across biology, immunoengineering, AI/machine learning and data science to generate insights into target biology and disease mechanisms, and translate these into actionable strategies and mechanisms to engineer and develop the right drug for the right patient.
Using cutting-edge computational biology tools, we build our understanding of the structure and function of proteins involved in disease mechanisms, then identify optimal therapeutic targets, strategies, and epitopes to precisely and effectively impact the disease.
How We Apply This
Our unique Rational Antibody Discovery platform enables us to overcome many of the challenges of finding potent therapeutic antibodies and to generate antibodies precisely engineered for efficacy, safety and developability. This includes the discovery of functional agonists and antagonists, antibodies against transmembrane proteins as well as the conserved regions of rapidly mutating e.g., viral proteins.
HOW WE APPLY THIS
Instead of relying on the response to the immunodominant regions of HER3 which unfortunately don’t overlap with the key functional interface required for dimerization, we specifically directed an immune response to the optimal yet elusive epitope on HER3 that our platform had identified. The resulting antibodies potently blocked HER3 activation to stop tumor cell growth.
HER3 is part of EGFR family of tyrosine kinase receptors which are key components of the MAPK and PI3K signaling pathways. It is frequently co-expressed, and forms dimers with other members of the protein family such as EGFR or HER2. This process can potently activate the PI3K pathway and leads to cancer cell proliferation and tumor growth. Several antibody therapies targeting HER3 have failed in clinical tests due to their inability to fully shut down HER3 signaling. By predicting and identifying the optimal epitope for antibody binding to prevent HER3 dimerization, Hummingbird has successfully developed an antibody against this elusive epitope. This novel mechanism of action of Hummingbird’s anti-HER3 antibody uniquely blocks all HER3 dimerization and activation, resulting in significantly more potent tumor growth inhibition, and the potential to prevent drug resistance.
Our translational mindset is grounded in a deep understanding of the mechanisms of disease, the causes of disease resistance and unmet medical need. We use human tissue studies, -omics and relevant disease models to test clearly defined hypotheses, both in our labs and in collaboration with academic and industry partners.
HOW WE APPLY THIS
In some patients and in some tumor types, treatment can fail due to upregulation of HER3 signaling. Through integrative analyses of robust datasets we are identifying biomarkers indicative of patient populations who may benefit most from HER3 therapy, for example, patients whose tumors carry neuregulin 1 (NRG1)-fusions.
We believe that clinical trials in precisely defined patient populations, leveraging novel biomarkers, innovative clinical methodologies and scientifically-driven hypotheses, can efficiently deliver clinical proof-of-concept for our programs.