OPRX-106 for for the Treatment of Inflammatory Diseases
About auto-immune-mediated disorders
Auto-immune-mediated inflammatory disorders are conditions that are characterized by common pathways that lead to inflammation and are caused or triggered by a compromised or dysregulation of the normal immune response. Immune-mediated inflammatory disorders can cause organ damage, and are associated with increased morbidity. Common auto-immune diseases include Rheumatoid Arthritis, Inflammatory Bowel Disease such as Ulcerative Colitis and Crohn’s Disease, psoriasis, and others. Some of the major treatments are anti-Tumor necrosis factor (anti-TNF) drugs, administered as subcutaneous injections or as intravenous infusions. Sales of anti-TNF drugs exceeded $30 billion annually.
OPRX-106 is a plant cell-expressed recombinant human tumor necrosis factor receptor II fused to an IgG1 Fc domain (TNFRII-Fc), in development for oral administration. When administered orally and while passing through the digestive tract, the plant cells function as a natural delivery vehicle, having the unique attribute of a cellulose cell wall which makes them resistant to degradation compared to proteins produced via mammalian cell expression.
Pre-Clinical Data and Clinical Studies
In November 2016, the first patient was enrolled in Protalix’s phase II clinical trial of OPRX-106 for the treatment of ulcerative colitis. OPRX-106 is a plant cell-expressed recombinant human tumor necrosis factor receptor II fused to an IgG1 Fc domain (TNFRII-Fc). The phase II clinical trial is a randomized, open label, 2-arm study of OPRX-106 in 20 patients with active mild to moderate ulcerative colitis. Patients will be randomized to receive 2 mg or 8 mg of OPRX-106 administered orally, once daily, for 8 weeks. The primary endpoint of the study is safety, including monitoring for adverse events following daily administration of the drug. Key efficacy endpoints include relevant disease parameters of the drug, including Mayo score and rectal bleeding. If successful, OPRX-106 will be the first ever oral enzyme treatment as currently there are no other oral enzyme treatments available.
In August 2015, we announced positive clinical study results from our Phase I clinical trial of OPRX-106. PRX-106 demonstrated a favorable safety and tolerability profile and biological activity in the gut. The phase I Clinical trial was a randomized, parallel-design, open-label study designed to evaluate the safety and pharmacokinetics of PRX-106 in healthy volunteers. The trial enrolled 14 subjects that were randomized to one of three dosing cohorts receiving PRX-106 doses equivalent to 2mg, 8mg or 16mg Tumor Necrosis Factor receptor-Fc fusion protein. Subjects received once daily oral administrations for five consecutive days. The results demonstrated that oral administration of PRX-106 is safe and well tolerated. No major side effects were noted, and no suppression of the immune system was observed. Regulatory T cell activation showing biological activity in the gut was observed. Fluorescence-activated cell sorting analysis (FACS) was performed using various antibodies for surface markers, and it was observed that all three dosages of PRX-106 promoted the induction of various subsets of T cells, some of which are correlated with anti-inflammatory response.
The efficacy of OPRX-106 was shown in preclinical studies using mouse models of immune-mediated diseases such as IBD (inflammatory bowel diseases) and immune-mediated hepatitis. Results showed that PRX-106 has the potential to positively affect these diseases, displaying changes in symptoms and in serum levels of anti-inflammatory markers.
Inflamatory Disease Animal Model
Oral Anti-tumor Necrosis Factor Alpha (anti TNF α) OPRX-106 for Inflammatory Diseases.
Potential to locally deliver higher doses with fewer side effects in an oral formulation