Theralase Lead Anti-Cancer Drug Effective in the Destruction of Brain Cancer when Activated by X-Rays
Toronto, Ontario (FSCwire) - Theralase Technologies Inc. (“Theralase®” or the “Company”) (TSXV: TLT) (OTCQX: TLTFF), a leading biotech company focused on the commercialization of medical lasers to eliminate pain and the development of Photo Dynamic Compounds (“PDCs”) to destroy cancer, announced today that its patented, lead anti-cancer drug, TLD-1433, when activated by X-rays, has been demonstrated preclinically, to be effective in the destruction of human GlioBlastoma Multiforme (“GBM”) cancer cells, a deadly form of brain cancer.
According to the American Brain Tumor Association:
“GBM are tumors that arise from astrocytes—the star-shaped cells that make up the “glue-like,” or supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cells reproduce quickly, being supported by a large network of blood vessels.”
“Nearly 80,000 new cases of primary brain tumors are expected to be diagnosed in the US this year, with approximately 32% of brain and central nervous system tumors presenting as malignant.”
“GBM represents 14.9% of all primary brain tumors and 55.4% of all gliomas. GBM has the highest number of cases of all malignant tumors, with an estimated 12,390 new cases predicted in 2017.”
“For adults with more aggressive GBM, treated with concurrent temozolamide (oral chemotherapy drug) and radiation therapy, median survival is about 14.6 months and two-year survival is 30%.”
“The first step in treating GBM is a procedure to make a diagnosis, relieve pressure on the brain, and safely remove as much tumor as possible through surgery. Because GBMs have finger-like tentacles, they are very difficult to completely remove. This is particularly true when they are growing near the parts of the brain that control important functions such as language and coordination. Radiation and chemotherapy may be used to slow the growth of tumors that cannot be removed with surgery. Chemotherapy may also be used to delay the need for radiation in young children.”
Theralase’s preclinical research is focused on determining whether its feasible that Rutherrin® (TLD-1433 + transferrin) injected IntraVenously (“IV”) into a patient diagnosed with GBM is able to fulfill the 4 criteria below:
Effectively cross the blood brain barrier and localize preferentially to GBM tumors
Once absorbed by the GBM tumors, safely and effectively destroy them, when activated by X-rays transcranially through the skull
Remove the need for surgical debridement
Complete the destruction of the GBM tumors at or below current standard of care radiation levels
In research conducted by Pavel Kaspler, Ph.D., Research Scientist and Manunatha Munegowda, Ph.D., Research Scientist, both of Theralase, under the direction of Arkady Mandel, MD, Ph.D., D.Sc., Chief Scientific Officer, Theralase, Rutherrin® has been demonstrated to possess the ability to selectively uptake into malignant GBM tumor cells (demonstrated in a rat RG2 cell-induced brain tumor model) over 22 times greater than in normal brain tissue, fulfilling criteria 1 above. (see Figure 1)
Figure 1. Rutherrin® uptake into RG2 cell-induced GBM tumor is highly selective, as verified by Inductively Coupled Plasma - Mass Spectrometry analysis 4 hours post Rutherrin® injection. (To view the graphic in its original size, please click here)
The GMB selectivity is believed to be due to the much higher expression of Transferrin Receptors (“TfR”) in brain tumors versus normal brain cells (approximately 10 times) (see Figures 2 to 4).
Figure 2. Expression of TfR is much higher in GBM than in normal brain tissue. (To view the graphic in its original size, please click here)
Figure 3. Cells positive for TfRs are more common in RG2 brain tumor than in normal tissue. Left panels show TfR immuno staining. Intensity of brown color of immuno staining indicates the intensity of TfR expression. Right panels show Hematoxylin and Eosin (“H&E”) staining again demonstrating greater TfR density in GBM tumor versus normal tissue. (To view the graphic in its original size, please click here)
Figure 4. Brain TfRs are predominantly localized in RG2 cells-induced GBM tumor (Left panel, dark brown staining). Neither healthy brain tissue outside of the tumor (Left panel) nor brain without tumor (Right panel) showed intense TfR staining. (To view the left graphic in its original size, please click here) (To view the right graphic in its original size, please click here)
TLD-1433 at a low dose (80 micromolar) has demonstrated an ability to be activated by X-ray (20 Gy, 225 keV) in human GBM (U87) cancer cells. At these X-ray radiation levels, GBM cell kill was approximately 75% versus negligible GBM cell kill with X-ray radiation alone, suggesting that cell kill was exclusively the result of TLD-1433 X-ray activation, fulfilling criteria 2 above.
Figure 5. High cell kill in GBM cells (U87) (measured by Presto Blue assay) by X-ray activated TLD-1433 versus negligible cell kill by X-ray alone. (To view the graphic in its original size, please click here)
Dr. Kaspler stated that, “This latest research data strongly supports that TLD-1433 would be effective in the destruction of human GBM cancer cells with a high safety margin. It is noteworthy that a high GBM cell kill by X-ray activated TLD-1433 was achieved at quantum energy levels significantly below that used clinically to treat GBM (225 keV versus 6 MeV, a 27 fold difference), suggesting a greater safety profile to healthy brain tissue during X-ray tumor treatment, fulfilling criteria 4 above.”
Dr. Mandel stated that, “TLD-1433 continues to advance preclinically and clinically in the destruction of new oncology targets. TLD-1433 GBM cell kill was observed at X-ray dosages of 20 Gy, that did not induce appreciable cell kill, without the presence of TLD-1433. This helps to confirm the phenomenon of radio-resistance of malignant GBM and suggests that this radio-resistance can be overcome by the X-ray irradiation of GBM tumor cells in the presence of TLD-1433. Given the potential benefit to improve tumor control, patient quality of life and survival, by combining an established method of radiation therapy, with an advanced radiation enhancer (TLD-1433), which modifies the tumor to become more sensitive to radiation therapy, is of high clinical interest and significance. The pre-clinical studies, completed to date, have shown antitumor synergy when TLD-1433 is combined with radiation therapy. This data conjointly, with a well-established manufacturing process for TLD-1433, and the strong safety profile observed in TLD-1433 treated patients in the on-going Phase Ib clinical study for Non-Muscle Invasive Bladder Cancer, looks even more exciting and calls for additional vigorous investigations into further experiments, which if successful, will lead to the design and commencement of a Phase Ib GBM clinical study.”
Roger Dumoulin-White, President and CEO of Theralase stated that, “This latest research confirms that the Company is on the right track to provide support for the design and commencement of a Phase Ib clinical study for patients inflicted with this deadly disease. Theralase will continue its research to identify if surgical debridement can be eliminated, fulfilling criteria 3 above. If a patient is able to receive an IV injection of Rutherrin® and then a specified number of hours later, after the PDC has been selectively absorbed into their GBM cancer cells versus normal brain cells, to receive X-ray activation transcranially, at levels at or below standard of care, providing for the safe and effective destruction of their GBM cancer, with minimum side effects, then this would be well worth the time and effort the Company has invested into this cutting-edge research.”
