Toronto, Ontario – June 11, 2018, Theralase Technologies Inc. (“Theralase®” or the “Company”) (TSXV: TLT) (OTCQX: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light activated Photo Dynamic Compounds (“PDCs”) and their associated drug formulations, intended to safely and effectively destroy cancer, has announced significant benefits of its Rutherrin® (TLD-1433 + transferrin) formulation in comparison to a clinically approved PDC Amino Levulinic Acid (“ALA”), in the destruction of Rat Glioma (“RG2”) brain tumours, representative of GlioBlastoma Multiforme (“GBM”), a deadly form of human brain cancer.
As previously disclosed, Theralase demonstrated that rats subjected to RG2 cancer cells, developed brain tumours representative of GBM. After intravenous (“IV”) injection of Rutherrin® and subsequent laser light activation, these animals survived significantly longer that animals who did not receive treatment and/or were treated with ALA-PDT.
Further research conducted by Theralase researchers has demonstrated that Rutherrin® is able to provide a significant (up to 400 %) improvement in survival in animals treated with Rutherrin® versus IV injection of ALA and subsequent laser light activation. (Figure 1)
Figure 1. Animal Survival Analysis (Kaplan-Meir)
Magnetic Resonance Imaging (“MRI”) data obtained from the pre-clinical experiments show that in the animals treated with Rutherrin® there was less non-specific inflammation in the brain as compared to ALA treated animals.
This observation is considered clinically advantageous; as excessive inflammation of brain tissue is known to cause post-treatment clinical complications, such as: lethal damage to brain tissue (cerebral death), bleeding in the brain and/or stroke due to increased intracranial pressure through the brain’s confinement in the skull. (Figure 2)
Figure 2. MRI data
Inductively Coupled Plasma Mass Spectrometry (“ICP-MS”), a type of mass spectrometry, which is capable of detecting PDCs in tissues at concentrations as low as one part in 1015 (part per quadrillion), demonstrated a significant RG2 (representative of GBM) specific PDC uptake, at 20-fold more in tumour versus normal (non-cancerous) brain tissue. Specific uptake by RG2 was investigated for various Rutherrin® doses and has been shown to be maintained for up to 20 hours in cancerous brain tissue commencing 4 hours post IV injection.
The highly specific uptake of Rutherrin® by RG2 tumours, provides an enhanced safety profile for Rutherrin® therapy and increases the time span over which a patient can be treated. It was shown that a 20-fold increase of Rutherrin® PDC in tumour versus healthy brain tissue enabled a higher tumour destruction, while reducing treatment related morbidity. (see Figure 3).
Figure 3: Rutherrin® Uptake Ratio (ICP-MS analysis)
Theralase researchers have also observed an increased number of anti-tumour specific immune cells in brain tissue treated with Rutherrin® versus ALA treated animals. This is quantified by observing the density of intratumoural, anti-cancer CD8+ T cells in GBM tumors. (Figure 4)
Clinical case studies of various cancers have demonstrated an increased survival in patients who possess a high density of intratumoural, anti-cancer CD8+ T cells in their respective tumours. It has been reported that an elevated level of tumour-infiltrating immune cells, such as anti- cancer CD8+ T cells, correlate with prolonged survival in GBM patients. (Justyna Kmiecik et. al Journal of Neuroimmunology 264 (2013) 71–83).
Figures 4. Immunohistochemistry slides and their computerized quantification bar graphs showing the recruitment of CD8+ T cells in the tumor microenvironment.
There are an estimated 24,000 new cases of malignant gliomas diagnosed in the US annually, with more than 14,000 deaths.
In the majority of the cases, they recur following initial treatment, especially for GBM, the most common and lethal form of brain cancer.
Manjunatha Ankathatti Munegowda, Ph.D., DVM, Research Scientist, Theralase stated that “In the current study, comparing Rutherrin® with the FDA approved PDC ALA, have shown the significant benefits of using Rutherrin® in this application. The safety aspects of Rutherrin® will be a game changer in clinics treating brain cancer due to: the significant selective uptake of Rutherrin® in cancerous tissue versus normal tissue, the comparatively reduced inflammation of brain tissue and the improved immune response of Rutherrin® treatments. All of these Rutherrin® characteristics would be extremely useful in targeting and eliminating any recurrences.”
There are an estimated 24,000 new cases of malignant gliomas diagnosed in the US annually, with more than 14,000 deaths.
In the majority of the cases, they recur following initial treatment, especially for GBM, the most common and lethal form of brain cancer.
Lothar Lilge, Ph.D., Professor, University of Toronto stated that, “Rutherrin® as a PDC for PDT, particularly in the brain region, has various critical and potentially life-saving benefits for GBM patients:
- The ability to use near infrared wavelength activation at clinical dose allows treatment of a much larger tumour volume than visible wavelength activated PDCs, such as ALA;
- A highly specific drug uptake ratio (cancerous versus healthy brain tissue) that allows aneurosurgeon the ability to extend the activation of Rutherrin® deep into the brain, enabling treatment of more complete “cancer affected” areas; including micro metastasis regions, that are unfortunately common in GBM patients, and are predominately responsible for cancer recurrence. The use of transferrin as the TLD-1433 delivery vehicle also allows an efficient and highly targeted drug delivery over the intact blood-brain barrier. An intact blood-brain barrier prevents the delivery of a majority of drugs including PDCs, but this issue has been circumvented by Rutherrin®.
- Reduction of inflammation post-PDT treatment with an increase in immune activity are further benefits to the survival of animals in tested pre-clinical models.
Taking all of these advantages together and translating them into the clinic has the highest potential to increase the median survival of GBM patients and increase the survival rate of patients well beyond 3 or even 5 years. Relapses are common in GBM patients, who are treated with FDA approved therapies, with a majority of patients not surviving beyond 2 years post- diagnosis. Terminally ill patients will be eligible for experimental drug therapies under a new Right to Try bill recently signed into law in the USA. Under this bill, we could potentially speed up clinical development of Rutherrin® for the treatment of life-threatening brain cancers.”
Arkady Mandel M.D., Ph.D., D.Sc., Interim CEO and Chief Scientific Officer, Theralase stated that, “The Company’s pre-clinical studies continue to show significant advantages of light activated Rutherrin® in the treatment of brain tumours, such as GBM. Building upon these encouraging results, we now can further optimise Theralase’s technology and improve its anti- tumour potency; including Rutherrin® induced specific, anti-tumour, CD8+ T-cells activity in the treatment of high-grade gliomas, such as GBM. Considering these strong pre-clinical results, Theralase will commence contacting clinical oncology neurosurgeons to join our Medical and Scientific Advisory Board to help design a clinical Phase Ib GBM clinical study for patients diagnosed with GBM with the intention to safely and effectively destroy their cancer with minimal side effects.”
About Theralase® Technologies Inc.
Theralase® is a clinical stage pharmaceutical company dedicated to the research and development of light activated compounds and their associated drug formulations with a primary objective of efficacy and a secondary objective of safety in the destruction of various cancers, bacteria and viruses.
Additional information is available at www.theralase.com and www.sedar.com
Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.
Forward Looking Statement
This news release contains “forward-looking statements” within the meaning of applicable Canadian securities laws. Such statements include, but are not limited to, statements regarding the Company’s proposed development plans with respect to Photo Dynamic Compounds and their drug formulations and a COVID-19 vaccine. Forward looking statements may be identified by the use of the words “may, “should“, “will“, “anticipates“, “believes“, “plans“, “expects“, and similar expressions including statements related to the current expectations of Company’s management for future research, development and commercialization of the Company’s COVID vaccine, including preclinical research, clinical studies and regulatory approvals.
These statements involve significant risks, uncertainties and assumptions; including, the ability of the Company to: adequately fund, and secure the requisite regulatory approvals to successfully complete clinical studies for a COVID-19 vaccine in a timely fashion and implement its development plans. Other risks include: the ability of the Company to successfully commercialize its drug formulations, the risk that access to sufficient capital to fund the Company’s operations may not be available or may not be available on terms that are commercially favorable to the Company, the risk that the Company’s drug formulations may not be effective against the diseases tested in its clinical studies, the risk that the Company’s fails to comply with the term of license agreements with third parties and as a result loses the right to use key intellectual property in its business, the Company’s ability to protect its intellectual property, the timing and success of submission, acceptance and approval of regulatory filings, and the impacts of public health crises, such as COVID-19. Many of these factors that will determine actual results are beyond the Company’s ability to control or predict.
Readers should not unduly rely on these forward- looking statements which are not a guarantee of future performance. There can be no assurance that forward looking statements will prove to be accurate as such forward looking statements involve known and unknown risks, uncertainties and other factors which may cause actual results or future events to differ materially from the forward looking statements.
Although the forward-looking statements contained in the press release are based upon what management currently believes to be reasonable assumptions, the Company cannot assure prospective investors that actual results, performance or achievements will be consistent with these forward-looking statements.
All forward-looking statements are made as of the date hereof and are subject to change. Except as required by law, the Company assumes no obligation to update such statements.
For More Information:
1.866.THE.LASE (843-5273)
416.699.LASE (5273)
www.theralase.com
Kristina Hachey, CPA
Chief Financial Officer
khachey@theralase.com
416.699.LASE (5273) x 224