Apitope® Technology Platform

The Apitope® (Antigen Processing Independent epiTOPE) technology platform enables the high-throughput screening of highly specific small peptide molecules to induce immune suppression specific to autoantigens, thus enabling targeted immunotherapy for various autoimmune diseases.

The goal of Apitopes® immunotherapy is to deliver Apitopes® to antigen-presenting cells (APCs), causing the expression of low levels of co-stimulatory factors. When T cells bind to the Apitope® presented by APCs and encounter low levels of co-stimulatory factors, the result is either the shutdown of T cells or their conversion into T regulatory cells. This leads to (i) the suppression of aggressive immune responses against self-antigens and (ii) the prevention of other immune cells from attacking the target antigen.

Worg currently holds exclusive global rights to all intellectual property and pipelines associated with the Apitope® platform and has completed the development and overseas clinical trials for multiple global First-in-Class (FIC) pipelines.

WP1303's major indication is Multiple Sclerosis (MS), a chronic, unpredictable and incurable disease of the central nervous system. Relapsing-remitting MS is the most common form of MS with 85% of new diagnoses. Most people are diagnosed with MS between the ages of 20 and 50, and the World Health Organization estimates that more than 2.5 million people suffer from MS worldwide (Haussleite I. et al., 2009).

WP1303 is the first potential therapeutic for MS that combines high efficacy with an excellent, and thereby differentiating, safety profile. Phase IIa study results demonstrated a significant reduction in total new and persisting lesions as well as the volume of lesions, and has showed a highly favorable and differentiating safety profile with zero treatment-related serious or severe adverse events across the 68 patients treated in clinical studies to date. Importantly, WP1303 halted progression of the disease and demonstrated a strong trend towards overall reduction in disability during the Phase IIa study, underpinned by a significant improvement in cognition after six months of treatment. Worg believes this constitutes one of the first reports of an improvement in cognition following immunotherapy in patients with MS based on their assessment of the market.

Most current treatments for MS globally suppress the immune system (thereby increasing the risk of life-threatening infections, cancers and other immune complications). The reduced relapse frequency and slowing of the progression of MS, comes at the cost of increased side effects resulting in a poor pay-off between efficacy and safety. WP1303 addresses the significant medical need for a high relapse reduction in combination with high tolerability, with the additional potential to improve cognitive disability in MS patients.

In addition to MS, the same peptide mixture of WP1303 could be indicated for MS-related Intermediate & Posterior Uveitis, and the relevant clinical investigation is at the stage of initiating Phase 2.

Graves’ disease is an autoimmune disease in which the immune system attacks the thyroid gland and causes it to become overactive. It causes overproduction of thyroid hormone leading to various symptoms such as, heat intolerance, sweating, weight loss, and muscle weakness. Thyroid eye disease which manifests as eye bulging is a frequent complication and associated with the potential risk of blindness. Graves' disease is one of the most common autoimmune diseases, with approximately 10 million patients across Europe and the US.

First line therapies for Graves’ disease consist of anti-thyroid drugs to reduce the production of thyroid hormones and/or radioactive iodine therapy. Many patients often fail current first line therapy, and the last remaining option is surgical removal of the thyroid, leading to lifelong thyroid replacement therapy and potential complications such as scarring and vocal cord damage.

Graves' disease provides fast market entry opportunities through rare and serious orphan indications with high unmet medical need including Graves' ophthalmopathy and pediatric Graves' disease.

WP1302 is the first treatment to target the immunological basis of Graves' disease and the first innovative treatment in more than 60 years for patients with the disease. WP1302 has been evaluated in a Phase I study in patients and is showing promising signs of early efficacy in the majority of patients with very favorable safety profile.

•Hemophilia A is a bleeding disorder caused by genetic mutations that result in absent or dysfunctional Factor VIII (“FVIII”), leading to inadequate clotting of the blood in response to any type of injury or surgery. Prophylactic treatment consists of regular intravenous FVIII infusions. Unfortunately, due to loss of tolerance by the immune system to FVIII, 1/4 to 1/3 of patients develop neutralizing anti-FVIII antibodies referred to clinically as “Factor VIII Inhibitors”. These inhibitors decrease the efficacy of FVIII and render the treatment ineffective, resulting in a serious bleeding diathesis. The management of patients with these inhibitors is complex and frequently requires increase in dose or dose frequency of factor VIII which increase the cost of therapy for these patients and the heath economic burden. Inhibitor development in non-Hemophilia A individuals also occurs as a rare but serious autoimmune reaction that is typically diagnosed subsequent to unexplained bleeding, primarily in the elderly, or following trauma, surgery or childbirth (Lacroix-Desmazes S et al., 2020). Currently, there are few therapies available to help Factor VIII Inhibitor patients.

WP1301 is a peptide derived from hFVIII with modifications to improve solubility which are capable of binding to an MHC class II molecule without further antigen processing and being recognized by a factor VIII specific T cell. WP1301 offers a potential first-in-class approach for both the treatment and prevention of Factor VIII Intolerance.

WP1301 has received EMA orphan drug designation and is about to enter clinical trials