ExoProTher Medical

Cancer is one of the major killers in the world; it accounts for nearly 1 in 6 deaths globally. While billions of dollars are being spent on cancer research, many cancers still do not have a cure, and the number of deaths from cancer is expected to continue rising in years to come.

The Need

About 60% of human cancers are caused by mutation in the gene encoding p53 protein. This protein is often referred to as ”guardian of the genome”. Damage to this mechanism leads to destruction of a cell's defense mechanism, and thus any further mutation can cause development of malignancy.The importance of p53 function has been known to scientists for decades, and many have tried to provide healthy human p53 to the cancer cells in order to repair the damage.  Still, up to date, no effective way to do so has been found.

The Solution

ExoProTher takes a completely novel approach to cancer therapy by using natural nano-particles - exosomes to deliver healthy p53 to malignant cells and restore the body’s natural tumor suppression function with minimal adverse effects.

Exosomes can easily penetrate the BBB (blood-brain barrier) and deliver treatment for glioblastoma (the deadliest kind of brain cancer) even by inhalation.

Initial indications pursued by the company target the deadliest cancer types with the highest rate of p53 mutation, such as brain cancer, lung cancer and colon cancer.

Harnessing Evolution to Fight Cancer: ExoProTher's nano-particles, which are the basis for the treatment, are harvested from tissues where cancer occurrence is extremely low. ExoProTher is, in fact, using an ancient biological mechanism that suppresses cancer development in immediate vicinity of these tissues turning it into a breakthrough systemic treatment applied to any location in the body.

It is important to note that exosomes are non-toxic and not immunogenic (do not trigger an immune response) and, therefore, do not cause side effects. EXO may reduce, and possibly even eliminate, the need for conventional treatments such as radiation and chemotherapy, which are so damaging to the body.

All of this makes ExoProTher's treatment revolutionary and the first of its kind in the world.

ExoProTher will be pursuing breakthrough therapy designation from the FDA and accelerated access to clinical trials.

The Technology

ExoProTher technology brings two major innovations:

Novel use of native nanoparticles – exosomes - as a vehicle to deliver p53 protein to cancer cells. The idea originates from a newly discovered mechanism that has existed for millions of years  in all vertebrates. It is widely known that malignant mutations can be caused by carcinogens, such as exposure to UV rays (ultraviolet radiation). Approximately 90% of skin cancers appear in sun exposed areas. Surprisingly, cancer development is extremely rare in the eyes, the organ also exposed to UV radiation. It turns out that in some tissues the amount of p53 protein, which prevents cancer development, is extremely high. In addition, in these tissues the p53, along with other tumor suppressors, is packed in exosomes capable of moving from cell to cell. Thus, if p53 in one cell in such tissue is damaged and does not protect it from further mutations, the cell receives healthy p53 from neighboring cells. ExoProTher researchers have proposed a unique way to produce and use exosomes loaded with active and healthy p53 as a breakthrough treatment for the most lethal cancers.

1. Only 26% of glioblastoma (GBM) cells remain viable following a single application of EXO.  
2. One of the biggest challenges in drug delivery to the brain is the blood-brain barrier (BBB) - a biological obstacle that makes it extremely difficult to treat brain cancers, such as glioblastoma. Professor Danny Offen from Tel Aviv University and Beilinson Hospital, an Israeli expert on exosomes and a scientific adviser to the company, mentions that, based on previous research, exosomes are able to pass the BBB and reach areas of the disease.
3. The graph above shows significant reduction of cancer cells viability following a single application of the therapeutic substance. (The experiment was conducted at the Integrated Cancer Prevention Center of the Souratsky Medical Center).

Exosome-based treatment is very attractive due to their native properties:

• Stable (stay in the system long enough to be effective)
• Non-toxic and non-immunogenic
• Able to pass BBB (blood-brain barrier), even using nasal inhalation
• Possesses natural ability to enter cells
• Can be used in conjunction with conventional treatments

Recently, the potential of exosomes as an oncology treatment delivery vehicle has been highlighted in a number of visionary papers. The technologies are still in an early stage of development and are being actively pursued by several companies. ExoProTher uniquely benefits from the experience of its scientific advisor, Prof. Daniel Offen, founder of successful cell therapy companies. Prof. Offen contributes expertise in exosome-based treatment accumulated in the field of neurodegenerative diseases.

2. Utilization of animal origin p53, instead of human. Use of animal origin protein solves one of the key problems hampering previous attempts of p53 function restoration. It has been found that even if one can deliver a healthy human p53 protein to cancer cells, it undergoes aggregation with the mutant protein and is unable to perform its function. The structure of animal protein is slightly different, preventing its connection with the mutant human protein but still allowing it to perform its designated function.It should be noted that multiple therapies derived from animal tissues have been previously approved by the FDA and are now widely used in a variety of therapeutic areas.

Experimental Results

ExoProTher has established a laboratory that serves as facility for production of the therapeutic material. In the course of preclinical studies the team worked with leading research laboratories in Israel.

In-Vitro Experiments (Cell Lines)

Efficacy of the treatment on glioblastoma, colon cancer, melanoma (skin cancer) and lung cancer was demonstrated in laboratory experiments.

After 24 hours, cancer cell death can clearly be seen in the control group, following the delivery of one dose of EXO_002 substance.

In-Vivo Experiment (animal testing) - Effectiveness and Toxicology

ExoProTher completed successful preclinical studies, results of which showed a doubling of life expectancy and reduction in metastases in colon cancer. A toxicity trial was also performed, showing a complete absence of side effects.