> APITOPE TECHNOLOGY

Worg is developing potential first-in-class antigen-specific immunotherapies by its novel discovery platform to select and develop highly specific peptide-based therapeutics, known as "Apitopes®" (antigen processing independent epitopes).

Apitopes®:

• are soluble, synthetic peptides based on human protein sequences.
• are designed to mimic naturally processed epitopes to restore the immune system's natural balance (i.e. tolerance to a self-antigen).

• selectively target only the immune cells that react to a specific antigen; modulating only the malfunctioning part of the immune system in order to avoid global immune suppression.
• treat autoimmune diseases at the earliest possible moment in the inflammatory immune response to prevent further tissue damage to the body.
• have the broad potential to treat a wide variety of autoimmune diseases.

Apitopes® treat autoimmune diseases (and other undesired immune responses) at the earliest possible moment in the inflammatory immune response to prevent further tissue damage to the body. Apitopes® are designed to mimic naturally processed epitopes to restore the immune system's natural balance (i.e. tolerance to a self-antigen). While current therapies for autoimmune diseases typically have the effect of suppressing the whole immune system, Apitopes® modulate only the malfunctioning part of the immune system in order to avoid such global immune suppression.

Apitopes® can be selected for the treatment of any autoimmune as well as other undesired immune responses (anti-drug antibodies) against biologic therapeutics. Worg is able to select and develop Apitopes® using its patented and cost-efficient discovery platform that enables the continuous selection of peptides that are likely to be safe and well tolerated.

The goal of Apitopes® immunotherapy is to direct Apitopes® to antigen presenting cells (“APCs”), which in the absence of a self-antigen to be processed, results in the expression of low levels of co-stimulatory molecules ("tolerogenic APCs"). When the T cell binds to the Apitope® presented by the APC and encounters insufficient levels of co-stimulatory molecules, the effect is to kill or switch off the T cell or convert the T cell into a regulatory cell (a "Treg cell) thereby (i) resulting in the absence or suppression of an aggressive immune response to the self-antigen and (ii) preventing other immune cells from attacking the antigen of interest.

The inflammatory immune response is triggered by activation of Th cells:

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Recognition of MHC II with co-stimulation induces active immune responses:

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Recognition of MHC II in absence of co-stimulation induces tolerance:

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