CHB-001 - A Novel Cancer Therapy

In addition to surgery, the main approaches used to treat cancer are chemotherapy and radiotherapy. Unfortunately, these treatments do not only affect cancerous cells, but can affect the body's healthy cells as well, and this is why there can be so many severe side effects associated with these treatments. However, more recently, new anticancer therapies have been developed that can specifically target cancerous cells, making them more effective, as well as having less side effects. Some of these new therapies try to harness the body's immune system to help fight the cancer.  Importantly, these new therapies demonstrate that if you have a drug which targets a specific aspect of cancer, you can achieve a safe and effective treatment. Unfortunately, many of these drugs are unable to enter the brain, and hence are not effective in targeting cancerous cells that have spread to the brain.

The role that inflammation plays in the progression of cancer has been well established. Inflammatory mediators can not only stimulate the proliferation of cancerous cells, but also help develop a blood supply for the growing tumour, and help facilitate the metastatic process. Ironically, these inflammatory mediators may also reduce the body's immune response to cancer, and help cancerous cells avoid programmed cell death (apoptosis). Multiple studies have shown that one particular inflammatory mediator, substance P, is over-expressed in many cancers, including breast cancer, and seems to play a key role in these processes that drive the progression of cancer. This same mediator also plays an important role in inflammatory responses within the brain.

The scientific team associated with Biotranslation have spent the last 25 years studying inflammation in the brain and looking at novel ways to control that inflammation. Their interest in brain cancer initially grew out of a desire to control the oedema associated with brain tumours. However, our research showed that inhibiting the inflammation associated with the tumours had a much wider reaching effect, and the drug was able to produce its own anti-tumour action. Treatment with a specific antagonist of substance P was able to cause regression of the tumour through both inhibiting the proliferation of cancerous cells and increasing the death of cancerous cells through apoptosis. Importantly, unlike steroids, inhibiting this mediator reduces inflammation, without causing immune suppression.

There is now a wealth of data that has been generated by both ourselves, and many respected international laboratories, that support the potential use of substance P antagonists as novel anti-tumour agents. To summarise the potential benefits:

• Substance P may play a role in systemic treatment failure, particularly with treatments, such as Herceptin
• Antagonists of substance P can inhibit tumour growth by preventing stimulation of the mitogen-activated protein kinase pathway
• Substance P can increase he expression of its own receptor in tumour cells, thereby enhancing its growth-promoting effects
• Antagonists of substance P may enhance apoptotic tumour cell death
• Antagonists of substance P may inhibit angiogenesis
• Antagonists of substance P may enhance immune protection against cancer by preventing substance P inhibiting natural killer cell activity
• Antagonists of substance P may help control peritumoural oedema

Whilst there is strong pre-clinical evidence to support the use of a substance P antagonist in cancer, this approach has been validated by our Senior Clinical Advisor, Dr Munoz. Through gaining approval for compassionate, off-label use of a substance P antagonist, he has been able to demonstrate its effectiveness in treating cancer patients, and he has successfully treated a small number of patients. The drug not only produced significant clinical benefits in terms of controlling the cancer, but also it was able to significantly reduce the side effects associated with either chemotherapy or radiotherapy.

In terms of developing a novel treatment, patient safety and positive patient outcomes must be the primary considerations. Whilst chemotherapy and radiotherapy are associated with significant side effects, they are a proven weapon in the fight against cancer. Hence, in terms of trialing CHB-01 as a novel anti-tumour therapy, our plan is to, at least initially, use it as an adjunct therapy. Importantly, it has been demonstrated that rather than interfering with either radiotherapy or chemotherapy, the antagonist can actually increase their anti-cancer activity. In addition, the use of a substance P antagonist can significantly decrease the serious side effects associated with these cancer treatments. For example, there is preclinical evidence to demonstrate that a substance P antagonist can help prevent the chemotherapy-induced cardiotoxicity associated with doxorubicin.

Again, patient safety is the primary concern when developing novel drug treatments. Indeed, safety concerns are often the reason why new drug treatments fail during development. In order to ensure success, Biotranslation have acquired an exclusive license from a major pharmaceutical company to develop and commercialize one of their drugs as an anti-cancer treatment. This drug, which was developed for another indication, has a demonstrated safety profile in humans, and is safe for long-term administration. It is also able to enter the brain in order to produce its beneficial effects. In addition, it has gained approval from the regulatory authorities as an investigational new drug.