Approach

At the core of our approach is a transformative R&D engine with which we advance the discovery and design of novel drug modalities for the treatment of cancer and other life-threatening diseases. These modalities make use of a range of molecular proximity and cooperativity mechanisms to facilitate selective engagement with traditionally challenging but well validated and high value disease targets. We apply our technological innovations to the discovery, design, and engineering of both small and large molecules, with emphasis on molecular glues and cytokine immunotherapies, respectively.

Cytokines

Cytokines are nature’s signaling messengers of the immune system and have very powerful immune regulatory activities. Their range and duration of action is therefore normally highly controlled. When engineering cytokines for therapeutic applications, imparting target selectivity is essential to avoid broad systemic cross-reactivities and tolerability limitations that have plagued traditional cytokine therapies.  Our technology provides new and effective solutions to the design and engineering of cytokines with high cell target selectivity and controlled activity range (A-Kines®). We have established this for multiple cytokine classes for modulation of various types of immune cells, and other cell types, as therapeutic approaches to cancer and other diseases.

Molecular Glues

Molecular glues are drug-like small molecules that act in unique fashion to modulate or dispose of disease target proteins by promoting their interaction with some other protein. Elimination of target proteins occurs by such protein complexes engaging nature’s conserved cellular protein degradation machineries. Our proprietary experimental, computational, and chemical methods support fully integrated discovery and optimization of such glues at large scale – including genome-scale assessment of target selectivity (across ~20,000 proteins). Our technology solutions enable us to approach many high-value but traditionally tough-to-drug disease targets. Our platform is largely target agnostic and has applications to virtually any disease indication.

Restoring the Cancer Immunity Cycle (CIC): Engaging innate and adaptive immune mechanisms

The CIC is a natural cycle of events that detects the presence of malignant cells in the body and orchestrates their destruction. Cancers grow and spread by generating an immune-suppressive tumor microenvironment (TME) that stalls the CIC. Our strategies involve overriding these cancer-imposed brakes across the different phases of the CIC.

Our programs are designed to modulate the CIC in multiple and synergistic ways, by invoking a diversity of targets, including cancer cells, immune cells, and other components of the tumor microenvironment (TME). It includes direct and indirect activation of tumor-killing T and NK cells through various mechanisms and signaling networks.

Orionis Technology Platforms

Molecular proximity and cooperativity mechanisms define mode of action of our drug modalities, and guide discovery, design, and engineering of our therapeutic candidates.

Learn about our platforms.

Restarting a Stalled CIC

Our programs target multiple stages and components of the CIC to restore immune attack against cancer – from detection of cancer cells to promoters of tumor antigen processing, T and NK cell activators, enhancers of immune cell infiltration, and inducers of T cell-mediated immunity.

Our strategies aim for single-agent activity, including in cancers that exhibit an intrinsically low or absent immune involvement, and thus are particularly challenging (i.e., cold tumors), and including cancers refractory to checkpoint inhibitors. Our technology and pipeline addresses virtually any type of solid or hematological cancer.

CIC Phase 1 - Detection

Antigen Presenting Cells (APCs) detect tumor antigens in necrotic tumor mass. Antigen uptake is associated with APC activation (priming).

Orionis Pipeline_SVGTumor Tumor antigens Primed APCAPC

CIC Phase 2 - Activation

Primed APCs activate and promote proliferation of tumor antigen-specific T cells (lymph node). Chemokines released from activated APCs act as chemotactic signals for recruitment of various immune cells (tumor).

Orionis Pipeline_SVGPrimedAPC Chemo tactic signals Immune cell T cellActivat ed T cell

CIC Phase 3 - Infiltration

Activated T cells (CTLs) reach and infiltrate tumor through tumor neovasculature. Multiple mechanisms regulate infiltration.

Artboard 1 copy 2Activated T-cellTumorBlood vessel

CIC Phase 4 - Killing

Infiltrated CTLs recognize and kill tumor cells. Activity of CTLs and viability of tumor cells is influenced by other cells and components of the tumor microenvironment (TME).

Orionis Pipeline_SVGSt r omal cell Immune cell

Desired outcome - Cancer immunity

Activated T cells may become memory T cells, which have the potential to impart long term cancer immunity.

Orionis Pipeline_SVGActivat ed T cell Activat ed T cell Memor y T cell