> 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 have multiple advantages:

1) Selective immune suppression:

Apitopes® are designed to mimic naturally processed T cell epitopes to restore the immune system's natural balance (i.e. tolerance to a self-antigen). Apitopes® selectively target the immune cells that react to a specific antigen; modulate only the malfunctioning part of the immune system and avoid global immune suppression.

2) Broad indication scope:

As the potential first-in-class antigen-specific immunotherapy, Apitopes® platform has broad potential to treat a wide variety of autoimmune diseases. In addition, Apitopes® can be the treatment for undesired immune responses, e.g. anti-drug antibodies against biologic therapeutics.

3) Proven efficacy:

Phase 2 clinical trials in multiple sclerosis and a phase 1 clinical trial in Graves’ disease have demonstrated efficacy of the respective Apitopes® treatments in these indications.

4) Excellent safety:

Over 80 patients were treated in clinical trials in two autoimmune diseases with excellent safety profiles.

5) Simple CMC:

Easy and scalable manufacture with short peptides (15-20 amino acid); simple formulation as peptide mixture in aqueous solution.

6) Established peptide design procedure:

The patented Apitopes® selection platform uses in silico, in vitro and in vivo models to select naturally processed T cell epitopes that induce antigen-specific immune tolerance.

7) Early treatment:

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.

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 Apitopes® 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:

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

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