Orionis has developed two transformative technology platforms. While technologically distinct, addressing small and large molecules, they both harness proximity and cooperativity mechanisms in drug mode of action. These innovations are leveraged to create precision medicines that engage with, modulate or dispose of disease targets with a high degree of selectivity, limiting off-target interactions and minimizing potential for drug liabilities.
Breakthroughs in Cytokine and Biologics Engineering
Cytokines are powerful immune regulators and attractive therapeutic effector candidates. However, their intrinsic pleiotropic activities have limited their therapeutic use. To achieve spatial control of cytokine action and avoid systemic toxicities associated with traditional cytokine modalities, we have evolved a proprietary biologics platform.
Our protein engineering solutions enable the creation of modified cytokines (A-Kines®), which exhibit highly restrained, conditional activity that is focused on cell targets of interest including immune cells, such as myeloid cells, T cells and NK cells, tumor cells, and many other components of tumor microenvironments. With such agents, we seek to effectively restore immune functions to trigger elimination of cancer cells and instill immunological memory and cancer immunity. We are developing a diversity of A-Kines to deliver effective, single-agent activity across a range of tumor types, including immunologically “cold” tumors, and tumors refractory to standard immune checkpoint inhibitors and other drug modalities. We are also evolving immunotherapy candidates with tolerability profiles that could open new avenues for early-stage disease treatments and management.
Given their unique modes of action and tolerability profiles, A-Kines also have substantial potential for combination with other drug modalities, including checkpoint inhibitors, radiation and radioligand therapies, targeted small molecules (including molecular glues), and cell therapies. A-Kines also have broad immune-regulatory applications to diseases other than cancer.
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
On target, conditionally acting cytokines
Rationally designed, multifunctional A-Kine therapeutics integrate cytokines modified to tune out off-target interactions and avoid systemic toxicities, while simultaneously promoting their own activation at targeted cells (top right). The result is precise delivery to and activation of cytokines at cell targets such as immune cells, cancer cells and components of tumor 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