Multivalent Constitutive Agonists
Often cell surface receptors require clustering to induce activation and effect downstream signaling. Receptors that require clustering are inherently difficult targets for conventional bivalent therapeutic antibodies, which are limited to interaction with no more than two receptors per molecule. In preclinical studies, we and third parties have observed that increased valency enhances receptor clustering and achieves the desired agonism of a target. We believe our ability to build multivalent therapeutic candidates will increase the potential to achieve clinical benefit by targeting these clustering-dependent receptors. Using our sdAb platform, we have developed higher order, multivalent antibodies that target TNFRSF agonists, as described below, that contain four (tetravalent) or six (hexavalent) antigen binding domains. Our multivalent therapeutic candidates are generally smaller than conventional antibodies and other multivalent formats that utilize fusions of natural ligands or immunoglobulin M-based constant regions, which we believe may confer advantages in the clinic.
Conditional Immune Activators
Through protein engineering, Inhibrx has developed innovative therapeutic formats to create conditional immune activation selectively in the suppressive tumor micro-environment. Inhibrx has applied its single domain antibody (sdAb) platform to expand the therapeutic window beyond that of conventional therapeutics against highly promising targets, where limited efficacy was observed due to the concurrent induction of systemic toxicities. The first of these efforts is a conditional 41BB agonist (INBRX-105).
Unique Protein Engineering
Inhibrx applies protein engineering to address specific liabilities of recombinant proteins and improve therapeutic function. Inhibrx created a recombinant Alpha-1 Antitrypsin fusion protein (INBRX-101) for Alpha-1 Disease with modifications to improve the pharmacokinetic profile (PK) and neutrophil elastase inhibitory function.