DESCRIPTION AND STATUS
PRTX-100, a natural compound, has been used in various FDA-approved extracorporeal immunoadsorption systems for both idiopathic thrombocytopenic purpura and rheumatoid arthritis.
The compound aims to restore normal immune system function by binding directly to the surface of monocytes (white blood cells responsible for phagocytosis [ingestion] of foreign substances in the body) and a subset of B-cells that are potentially involved in the development and progression of certain autoimmune diseases, including rheumatoid arthritis. This mechanism of action allows PRTX-100 to modulate the function of these cells and restore balance back to the patient’s immune system.
Since PRTX-100 is expected to require significantly lower dosing than current therapies and may not necessitate long-term administration due to its demonstrated persisting effects, this compound represents a potentially important new therapy for rheumatoid arthritis. Management believes that upon approval, PRTX-100 would initially be used in patients with severe cases of rheumatoid arthritis, particularly for those individuals for whom other treatments have failed.
When tested in autoimmune disease models, PRTX-100 was able to reverse the pathologic process, resulting in restoration and maintenance of normal, healthy tissue. Preclinical studies completed by Protalex indicate that extremely low doses of PRTX-100 have efficacy equal to or better than the approved biologic etanercept (Enbrel®), an available treatment for rheumatoid arthritis, but with fewer projected side effects. PRTX-100 has proven effective in clinical standard mouse autoimmune models, including:
Collagen-Induced Arthritis
PRTX-100 has demonstrated reproducible efficacy in a well-established animal model of rheumatoid arthritis. In this model, mice received two injections of collagen in order to stimulate an inflammatory response. One group was treated with various doses of PRTX-100, a second group received etanercept (Enbrel®), a leading commercially available treatment for rheumatoid arthritis, and the control group was injected with vehicle saline solution. The mice were observed for clinical symptoms, joint size and loss of function. The results showed that very low doses of PRTX-100 and standard doses of etanercept (Enbrel®) suppressed clinical symptoms, including joint swelling, over the first two to three weeks of treatment, and slowed disease progression as compared with the control group. Thereafter, the PRTX-100-treated mice continued to remain disease-free, whereas the mice treated with etanercept (Enbrel®) showed a resumption of joint inflammation and tissue damage. This response to etanercept (Enbrel®) was expected because the mice developed immune response to it because it is a foreign protein. Overall, these results indicate that PRTX-100 is a potential treatment for rheumatoid arthritis in humans. These results were reported in November 2006, at the Fifth International Conference on Autoimmunity, in Sorrento, Italy.
Completed pre-clinical safety studies in animals have shown no drug-related toxicity. In a safety study conducted in New Zealand white rabbits, all of the animals in this study survived. No differences were observed in body weight gain or food consumption, nor in hematology, clinical chemistry, urinalysis, or organ weight data in animals treated with PRTX-100 compared with controls treated with vehicle, or the same dilutive material, less PRTX-100. These data were a crucial component of the Company’s March 2005 Investigational New Device (IND) application with the FDA, which was subsequently approved.
Additional studies in non-human primates to determine the pharmacokinetics of PRTX-100 have indicated more favorable dosing schedules. Since non-human primates are more closely related to humans, Protalex performed additional toxicology studies in monkeys to establish the toxicity and starting doses in humans.