The Proprietary Nano-Particle Technology FAQs

The Versamune™ technology is based on biodegradable lipid nanoparticles possessing a positive charge. By formulating a disease-associated protein or peptide (antigen) within the particles, the nanoparticles facilitate uptake of the antigen by the antigen presenting cells of the immune system. The nanoparticles simultaneously stimulate the immune system (act as an adjuvant) to generate a strong and specific response against the cells in the body infected with or expressing the particular protein or peptide. The result is a potent immune response resulting in eradication of the specific cancerous or diseased cells.

An antigen is any foreign agent, usually a protein or peptide (very small protein), which stimulates the body’s immune system to react in order to eliminate or neutralize the agent.

Unlike typical cancer and infectious disease drugs which are developed to target and kill cancer cells or infectious agents, and often have toxic side-effects on normal tissues, Versamune™ primes the body’s own immune system to mount a potent response targeted at the specific diseased cells (based on the formulated antigen), resulting in eradication of the disease.

By formulating the antigen with the nanoparticles, efficient uptake of the disease-associated protein or peptide by the antigen presenting cells of the immune system is facilitated. Therefore Versamune™ overcomes a major obstacle in the development of effective immunotherapies, which is rapid elimination of proteins and peptides from the blood circulation upon injection resulting in poor uptake by the immune system.

Secondly, Versamune™ acts as a safe immune stimulator (antigen) leading to very simple, cost effective and potent formulations.

The mammalian immune system responds to antigens. For an immune response to occur the antigen must be taken up by special cells known as antigen presenting cells (APC). Dendritic cells are the most potent antigen presenting cells. The APC must then become activated and present the antigen to the T-lymphocytes of the immune system also known as T-cells.

Two types of T-cells can then be activated and induced to proliferate.

1. Helper T-cells which are involved in activating and directing other immune cells. They are essential in determining antibody activity, and in maximizing the bactericidal activity of other immune cells such as macrophages.
2. Cytolytic T- lymphocytes also called killer T-cells, which attack cells infected with foreign agents, leading to eradication of disease.

Often the antigen may not be effectively presented to the APC, and/or T-cell proliferation may not occur efficiently, leading to a poor immune response to disease. In the case of cancer, certain cells, known as T-regulatory cells, are also believed to involved with suppressing a strong immune response.

Versamune™ operates by a unique dual mechanism. The technology is very efficient not only in presenting the antigen into the cytoplasm of the antigen presenting cells (APC) of the immune system, but also in activating the immune cells. Versamune™ stimulates the immune system to produce critical substances known as cytokines and chemokines. These substances are critical to the immune system’s ability to recruit APC and T-cells (the effector cells of the immune system), and also enhance T-cell proliferation as well as the cytolytic function of the killer T-cells. The result is efficient eradication of the particular disease associated with the antigen. Versamune™ has been shown to be equally effective with protein or peptide antigens.

PDS’s studies have shown that the ability to activate the dendritic cells (the most potent APC) and stimulate the immune system is specific to certain positively charged lipids possessing specific structures. Several zwitterionic, neutral and negatively charged lipids were shown not to have the capability to activate the immune system.

Other adjuvants are in use in vaccines and immunotherapies such as aluminum hydroxide, aluminum phosphate and montanide. A number of bacteria-derived adjuvants are also in clinical trials. However, the signaling mechanism by which Versamune™ activates the immune system differs from that of other adjuvants and minimizes toxic inflammation thus placing it in a unique class of safe, yet potent immune stimulators (adjuvants).

Versamune™ has been evaluated in cancer models in animals. PDS’s lead product is being developed to treat cancers caused by infection with the human papillomavirus (HPV). The product is Versamune™ - HPV. Complete regression of the cancer has been demonstrated. The technology is equally effective when used as a preventative prophylactic vaccine. Complete prevention of the cancer was demonstrated in the treated animals.

The mechanism of action has been established in human model studies. Human model studies have demonstrated high efficacy of Versamune™ in activating the human immune system to target disease and kill infected cells with respect to the formulated antigen.

The ability to evaluate efficacy and to optimize the formulation in human models significantly increases the likelihood of success in clinical trials, and distinguishes PDS Biotechnology Corporation from other cancer / infectious disease therapeutic companies at this stage.

Significant progress has been made in understanding the immune system and biology of disease. A few biotechnology companies including ours are applying this knowledge to the development of more effective drugs.

What makes Versamune™-based drugs unique is the dual function of the Versamune™ nanoparticle technology which efficiently delivers the foreign antigen to the immune system and simultaneously efficiently stimulates the immune system to induce the production of critical chemicals thus enabling the body to generate a strong and specific cytolytic T lymphocyte (killer T-cell) response. This potent CTL response is directed against the cells infected with the target antigen. The result is very simple, safe, cost effective and potent therapies.

Other lipid-based formulations in development are significantly more complex and expenisve as a result of the need to incorporate additional immunostimulators in an attempt to stimulate an immune response. Most other immunotherapies in development utilize adjuvants which stimulate the immune system via the nuclear factor kappa B (NF-kB) signaling pathway, leading to the production of pro-inflammatory cytokines. Versamune™ has been shown to stimulate the immune system via a mitogen-activated protein kinase (MAP Kinase) signaling pathway, which does not induce the production of certain pro-inflammatory cytokines. Safety is therefore improved over competing technologies.

Datamonitor predicts that by the year 2012, the market for cancer immunotherapies will exceed $8 billion.

Positively charged lipids have been used in gene therapy and the development of DNA vaccines. Although none of these gene therapy drugs have yet to be commercialized, several have successfully gone through human safety clinical trials demonstrating their safety.

A number of tumor associated antigens specific to various types of cancer would be suitable for use in the technology. Some examples of such cancers are ovarian cancer, melanoma, colorectal cancer, pancreatic cancer, non-small lung cell carcinoma and breast cancer.

Antigens derived from infectious pathogens known to cause other cancers may also be included in the formulation of the cationic delivery system. It is estimated that about 20% of the worldwide incidence of cancer can be attributed to infectious pathogens. Some examples of such cancers are cervical cancer, head and neck cancer and anal cancer.

The technology is also being applied to the development of immunotherapies to cure and to prevent viral diseases. Pathogens which may be targeted include viruses, bacteria etc. Examples of viral pathogens include, Retroviridae (HIV-1), Herpes simplex virus, Picornaviridae (e.g. polio viruses, hepatitis A viruses etc.), and Orthomyxoviridae (e.g. influenza viruses) to name a few.

Safety. PDS Biotechnology Corporation’s products in development consist of a simple formulation consisting of the biodegradable Versamune™ nanoparticles and the antigen. Demonstrated high potency allows for very small amounts of the formulation to be administered. Unlike other studied adjuvants, Versamune™ does not induce significant production of pro-inflamatory cytokines, further improving safety. The immune responses generated are specific to the diseased cells (due to antigen). The above factors should result in few side effects compared to other competing products.

Wide Applicability. The Versamune™ technology has broad applicability in the development of novel immunotherapies for the cure of various cancers and infectious diseases. The technology also has utility in the development of vaccines to prevent multiple chronic diseases.

Convenience. All product candidates are intended to be administered via injection on an outpatient basis.

Potency. The Versamune™ technology efficiently targets the antigen presenting cells of the immune system and generates potent T-cell immune responses against cells expressing the encapsulated antigen.

Production. The simple 2-component formulations are simple and less expensive to manufacture.