Pharmaceutical Development

The immune system 

The body’s immune system consists of a large number of white blood cells that protect against disease. Together they constitute the immune system— 2-3% of the body’s weight—which extends throughout the body, although mostly in surface tissue. As many as two-thirds of all immune cells are found in the intestines. 

It is customary to describe the immune system as two different systems: One is called the innate immune system, the other the adaptive immune system. 

The first is already fully developed at birth. Similar systems are found in all animal species. These systems function as the first line of defense and respond swiftly to arrest most infections. The white blood cells that constitute the innate human immune system are equipped with biochemical killer mechanisms that can destroy microorganisms and cancer cells. They also play the main role in eliminating dead cells from the body and in repairing damaged tissue. 

The adaptive immune system is activated when an infection is about to overpower the defense mechanisms of the innate system. It takes a week or more for the white blood cells that belong to this system to begin producing antibodies against microorganisms that have succeeded in penetrating the outer defenses. But if the same infection recurs, this system responds swiftly and effectively. It “remembers” previous infections and strikes back immediately if an infection recurs. This is the basis of vaccination: protection against later infection by giving the body substances (antigens) that are specific to a particularly dangerous organism, and to which the immune system reacts as if an infection were present. The innate immune system functions as a central regulatory and monitoring system for the body’s total immune defense.  Via its action on the innate system, the adaptive system can, for example, be regulated to improve the efficiency of vaccines. The action on the innate system can also be regulated to have an inhibiting effect on immune reactions so that otherwise dangerous inflammations are held in check. 

Biotec Pharmacon has based its pharmaceutical development program on research into how the innate immune system functions and how beta-1,3/1,6-glucan SBG can strengthen or suppress immune reactions. The action of the innate immune system when SBG is administered affects quite fundamental immune mechanisms that, in turn, can affect many different pathological conditions. For millions of years, animals and humans have made use of a chemical structure corresponding to SBG as a general alarm signal for mobilizing the immune system’s fight against infections. We now know that white cells such as macrophages, dendrite cells, natural killer cells, and granulocytes, which are all part of the innate immune system, are equipped with quite special surface structures called receptors that bind SBG. Not only does the binding of SBG to white blood cells in the skin and mucosa result in a general mobilization of defenses against infection, it also strengthens the body’s ability to repair tissue damage and create new tissue and triggers mechanisms that are active in killing cancer cells. Biotec Pharmacon has given high priority to the treatment of diabetic ulcers and to the immunotherapy of cancer in its pharmaceutical development program. Due to SBG’s effect on fundamental mechanisms in the innate immune system, the product will also be of potential use in other clinical indication areas. 

Treatment of ulcers 

Skin wounds usually heal without complications in humans with well-functioning immune systems. The white blood cells in the skin’s connective tissue, especially macrophages, play a key role in normal wound healing. We have found that the functioning of these cells is impaired in diabetics, which may explain why diabetics, more than other persons get ulcers that do not heal. The effect of SBG on this disease is based on knowledge of the mode of action of this substance. This knowledge was the reason for the company’s decision to give priority to the treatment of diabetics in its pharmaceutical development program. The first studies with a limited number of patients, carried out in Archangelsk in Russia, yielded very good results and created the confidence needed for the company’s decision to go ahead with a big clinical phase II study in this area. In 2006, the phase II study was conducted in Archangelsk and St. Petersburg on a total of 60 patients. The study yielded good results compared to studies with the best preparations available on the market. The results were not statistically significant after twelve weeks of treatment (primary end point), but additional non-prespecified analyses showed statistically significant differences in favor of SBG after eight weeks of treatment. This is important because the greatest portion of the costs of treating diabetic ulcers is the number of days a patient must spend lying in a hospital. A phase II (b) study with 120 patients to verify the results of the phase II study has just been started in England. 

Oral mucositis 

In 2006, the company completed a clinical phase II study with SBG on patients with cancer of the skin and throat regions to prevent the development of oral mucositis (formation of necrotic ulcers in the oral mucosa) as a consequence of radiation treatment. The study yielded clear indications that SBG can prevent the development of oral mucositis in this patient group, and a new follow-up study to verify these findings is being planned. Biotec Pharmacon has been given a so-called “orphan drug” status by the European Medicines Agency (EMEA) for the use of SBG in this treatment. 

Cancer immunotherapy

Cancer is a disease in which abnormal tissue cells begin to multiply out of control to produce tumors. Cancer immunotherapy is based on the idea of helping the body’s own immune system to detect cancer cells and kill them. There are two different approaches to get the immune system to combat cancer on its own. The first is to vaccinate with substances (antigens) found in cancer cells for the purpose of getting the body to produce its own antibodies against these cells. This principle may be compared with normal vaccination against infectious disease. The other approach is to inject ready-made cancer antibodies. The latter method has become quite popular in the past 5-10 years after it became possible to create human antibodies in the laboratory with the aid of modern biotechnological methods. However, common to both methods is that the clinical efficacy has proven to be lower than expected. Nonetheless, the use of antibodies — the so-called monoclonal antibodies (mAbs) - against cancer has seen extremely rapid development over the past five years and the sales of mAbs against cancer was more than NOK 40 thousand million in 2005.

Model studies on animals done at the Memorial Sloan Kettering Cancer Center in New York have shown that Biotec Pharmacon’s soluble beta glucan product SBG in combination with injected antibodies against cancer has a much better effect than antibodies administered alone. It is assumed that SBG contributes specifically toward directing the immune system’s killer mechanisms against cancer cells marked by the injected antigens. This was the basis of the first clinical phase I/II study in which SBG was administered in combination with a cancer antibody to children with neuroblastoma (a type of cancer originating in the nervous system). The purpose of the study is to find a suitable and safe dose of SBG, as well as any clinical efficiency. The study was started in October 2005 and is expected to be completed in 2007 after being expanded to a total of twenty-four patients and two higher dose levels. The study was enlarged because the original highest dose planned caused no notable side effects and promising therapeutic effects were observed. 

Biotec Pharmacon has recently started a phase I/II study in which SBG will be tested in combination with injected antibodies (Trastuzamab/Herceptin) against breast cancer in women. This study is being carried out as a multicentre study at the Ullevaal University Hospital, the University Hospital in Tromsø, and the Ålesund Hospital. A phase I/II study in which SBG will be administered orally in combination with Ritximad/Riuxan against non-Hodgkins lymphoma is being planned for the Radium Hospital/Rikshospitalet. In both cases, the antibodies are directed against structures (antigens) found on cancer cells, and it is hoped that these structures will function as sites of action for killer cells mobilized by SBG. 

The company has also entered into an agreement with the Charité University Hospital in Berlin to carry out basic studies of the cellular and molecular mechanisms behind SBG’s effect against cancer.  

An important business opportunity for the company lies in SBG's ability to improve the clinical efficacy of vaccination, or cancer antibodies. Despite the high sales figures of such antibodies cost-benefit evaluations indicate that their application is limited. A single treatment with mAbs can cost several hundred thousand Norwegian crowns per treatment, yet its life-prolonging capability is very limited. If the effect can be improved economic objections will be fewer.