Orionis has developed multiple technology platforms for the discovery of new generations of therapeutics and precision medicines whose pharmacological activities are directed by design to disease targets, avoiding undesired off-target interactions and potentially associated drug liabilities. Our technology platforms further enable access to a broad range of target types to address multiple key disease vulnerabilities for the development of novel therapies.
A breakthrough in cytokine drug development
Harnessing the intrinsic functions of cytokines as key regulators of the immune system and natural defense against cancer.
Cytokines, such as interferons, tumor necrosis factors and interleukins, are powerful regulators of the immune system and attractive therapeutic effector candidates – provided that their sites of action can be restricted to avoid systemic exposure and toxicity. To achieve such spatial control of cytokine bioactivity upon drug administration, we have evolved a proprietary biologics platform that integrates a strategic “plug-and-play” assembly of modular, biomolecular building blocks into therapeutic agents with unique conditional effector functions and cell target selectivity.
Using our design principles and platform capabilities, we have engineered monomeric to trimeric cytokine effector molecules that exhibit highly restrained and conditional activity that can be activated upon interaction with the target cell. To facilitate such cell interaction, we developed an arsenal of compatible cell-targeting modules that can undergo coordinated assembly into A-Kine™ therapeutic agents with applications in cancer and other diseases.
Standard (natural) cytokine
Schematic of a 4 alpha-helical bundle cytokine. The cytokine has high affinity for its natural receptor expressed on many cell types throughout the human body
Modified cytokine engineered to exhibit low intrinsic affinity and activity towards its natural receptor
Interaction of a modified designer cytokine with its natural receptor on intended target cell is restored upon binding of a linked targeting module to a target cell-specific surface biomarker
Reprogramming cell target
Rationally designed, multifunctional A-Kine™ therapeutics integrate cytokines that are modified to tune out OFF-Target interactions and associated toxicities while simultaneously promoting their own activation at intended target cells (ON-Targets). The result is precise delivery of their biological programming codes to targets such as immune cells, cancer cells and components of tumor or other disease microenvironments.
A-Kine™ biologics are disease target-focused
Natural cytokines can cause adverse effects and systemic toxicities through interaction with a wide range of cell types in different tissues. In contrast, activity of A-Kine™ biologics is disease target-focused
Modular portfolio of A-Kine™ biologics
Illustration of plug-and-play assembly of A-Kine™ biologics with variable types of designer cytokines and cell targeting modules