Platforms

Orionis has developed three transformative technology platforms.

While technologically distinct, addressing small and large molecules, they all 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.

Allo-Glue® Platform

Transformative Small Molecule Glue Discovery & Design

AlloGlues® are small molecule monovalent glues that induce or enhance specific protein-protein interactions by reprogramming protein functions and impacting disease targets through either proximal or distal allosteric mechanisms, including targets once considered “undruggable”. Outcomes of induced proximity include target protein degradation, inhibition, modulation or stabilization. Our fully integrated platform replaces binary and serendipitous discovery with systematic, large-scale discovery, design and optimization of diverse monovalent glues.

Key Features of the Allo-Glue® Platform
The platform integrates multiple technologies that enable molecular interaction complexity to be studied in several dimensions, including:

  • Scale and speed in experimental and in-silico data acquisition: large-scale discovery and analysis of protein-protein interactions in living cells by integrating proprietary biological assays with custom automation, robotics, specialized numerical modeling and OrionisBio™ AI/ML tools
  • Discovery modes: target-centric, reverse target-centric and ligase-centric approaches enabled at scale
  • Chemical diversity: scaffold diversity in our compound libraries enables the exploration of large chemical space
  • Specialized Orionis SAR-Enhancer AI: proprietary tools that enable multivariate in-silico interrogation of virtual but readily synthesizable compound space comprising over a trillion molecules – driving rapid SAR and glue optimization cycles
  • Protein diversity: empowers interrogation paradigms across ~20,000 proteins (genome-scale) and hundreds of qualified ligases to assess glue-responsive protein interactions in living cells

General drug discovery applications: the platform can support drug discovery and optimization paradigms across virtually any small molecule and target type. This includes genome/proteome-scale assessment of drug-protein interactions.

Molecular glue actions and dimensions

A-Kine® Platform

New Generation of Immune Modulators

Cytokines are powerful, short-lived immune regulators that generally act in vivo in close range of cells that produce and secrete them. They are highly attractive therapeutic effector molecules that play key roles in immune-mediated protection against viral infections and cancer. Examples include interferons, interleukins and tumor necrosis factors. Systemic delivery is, however, associated with substantial toxicities due to their interactions with many cell types across many tissues and organs. We address this liability by re-engineering cytokines to impart high cell target selectivity.

A-Kines® are rationally engineered cytokines, designed for selective activity on specific disease targets. Using structure-based design and multiple functional cues, we tune cytokine activity to avoid off-target interactions while enabling localized, in-cis activation on target immune or tumor cells. This approach preserves on-target potency while reducing the systemic toxicity seen with traditional cytokine therapies.

Key Features of the A-Kine® Platform include:

  • Improved safety: Engineered to remain inactive until they reach target cells, enabling precise and potent in-cis on-target signaling while minimizing off-target interactions
  • Modular and flexible: Built as a plug-and-play platform with tunable targeting and effector modules grafted on specialized scaffold frameworks
  • Broad compatibility: Applicable across multiple cytokine classes, as demonstrated for interferons, interleukins and tumor necrosis factors
  • High developability: Engineered to overcome scalability and developability challenges traditionally encountered with cytokine modalities

Plug & Play assembly of A-Kine® biologics

MCE Cell Engager Platform

Novel Approaches to Cell-Cell Interactions

MCEs are modular biologics that connect immune and tumor cells to deliver tailored immune responses. Our cell engager platform leverages a similar engineering foundation as our clinical-stage A-Kine® technology. MCEs are designed to mediate highly specific interactions between immune cells, tumor cells, and cells within the tumor microenvironment (TME). By combining precision targeting with modular effector functions, our cell engagers offer a flexible framework for tailorable anti-tumor responses.

Key features of the MCE platform include:

  • Effector-less scaffolds and tunable linkers: Frameworks built for control, plug-and-play assembly and flexible in vivo half-life management
  • Precision targeting modules: Specialized antibodies and ligands that bind to selective sites on immune or tumor cells
  • Custom effector modules: Inclusion of specialized modules—such as our proprietary A-Kines®—to tailor immune activation and functional outcomes
  • Versatile engagement classes: Designed and developed to empower activation or reprogramming of various immune cells and pathways, including: CD8+ T cell engagers, NK cell engagers, Myeloid cell engagers, Tumor cell engagers, and other TME cell engagers

Cell Engager formats