Gustoes wrote: Phase II ACT-NMIBC study I think think this is the first reference to "ACT-NMIBC"
Previous reference was "
Phase Ib Non-Muscle Invasive Bladder Cancer (“NMIBC”)" We all need to ACT like ACT, is a big deal. :)
but be patient as well.... ACT+TLD1433, first impressions are everything!
Phase II from what I can see, is entering a new world for our potential.
Anti Cancer Treament
Anti Cancer Technology
Anti Cancer Therapy
The Company’s primary technology is ACT, which is the preclinical and clinical research and development of PDCs and the laser light systems that activate them, primarily intended for the destruction of specific cancers.
TLC3200 Medical Laser System, Laser Emitter (“TLC3203”) and Laser Detector (“TLC3204”).
PH2 presser said: "The Company has focused its engineering resources on upgrading the TLC-3200 medical laser system based on clinical feedback gained in the Company's successfully completed Phase Ib study. We are excited to introduce this next level technology into the Phase II ACT-NMIBC study."
It looks like this was already approved but still, they made good use of their time with upgrades.
Health Canada has granted the Company Investigational Testing Authorization (“ITA”) approval (in December 2018) to utilize its patent pending TLC3200 PDT Laser System, in conjunction with its Clinical Trial Application (“CTA”) approved lead PDC, TLD1433 (in November, 2018), to commence enrolling and treating patients in Study II
In April, 2019 the University Health Network Research Ethics Board (“UHNREB”) approved the commencement of Study II.
As Fred mentioned: This suggests that the upgraded 3200 was the subject of the recent ITA and is therefore already approved. (DEC 2018)
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The ACT technology is currently under clinical development and as a result there are no commercial benefits associated with this Division at the present time, resulting in no revenue, sales or distribution of this technology.
Theralase conducts its own research and development into this technology, as well as enlisting the support of external scientific, research, regulatory and clinical organizations.
"FDA GUIDELINES"
See "February 12, 2018, FDA issued final guidance on developing drugs and biologics for treatment of bacillus Calmette-Gurin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC"
The estimated timing of completion of Study II is approximately 3 years from regulatory approval(s), but may vary significantly depending on numerous factors including: number of oncology sites, oncology site patient enrollment rates, patient compliance, treatment success and/or successful achievement of clinical Study II endpoints.
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I hope they take as long as they need to execute. It's all about execution and top notch advances and results. I'm happy with any delays they take to develop the patient screening, hardware, software and planning and procedure. It is critical. However, with great execution and great results,, those first results could paint an accelerated picture pretty easily.
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Per previous from fred and quattro questions and observations.
Kipton Lade, B.Sc., M.Sc., MBA, CEO - Device Division, Theralase stated that, "The Company has focused its engineering resources on upgrading the TLC-3200 medical laser system based on clinical feedback gained in the Company's successfully completed Phase Ib study. We are excited to introduce this next level technology into the Phase II ACT-NMIBC study.”
This suggests that the upgraded 3200 was the subject of the recent ITA and is therefore already approved.
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It is now clear that a large element of the delay between Phase I and Phase II is explained by the imperative to develop and gain approval for the upgraded 3200 laser. My belief is that this had nothing to do with the DFOC but derived from the lesson learnt in Phase IB that more power (which I take to mean light intensity) was required both to achieve efficacy and to eliminate the need for the very long treatment times that it appears to have been taking to deliver the therapeutic dose. This would also explain the delay between 4 and 5 in Phase IB - when the problem was first understood and initially addressed - and the consequent superlative results for 5 and 6. If so this has very positive implications for the Company well beyond NMIBC. There is much low-hanging fruit in terms of superficial head neck gullet and gynae cancers that would require only TLD-1433 and not Rutherrin provided that the means of activation were up to the quality of the PDC. If this is what TLT has achieved in this interval then it will have been well worth the wait. ================
YES. Just need to get ACT/TLD1433 in the door.
GMB or other news would be great for spirits.
Nasdaq for proper speculation or valuation would be ideal.
but it really comes down to opening doors, then see what is behind them
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I'm not an expert, just a dot connector or dreamer.
I look at the long game and glitches in the matrix.
I bought 100,000 shares of Garibaldi at 10cents not because it was the next Voisy Bay but because it could have been.
Who wouldn't want to be part of bringing a volcano back to life again?
The risk is not even close to my junior resource dabbling with GGI.
They've fallen back to earth but they were nothing more than land requiring cores to see what was there. Where as TLT is a whole lot of core, just need land!!
I look at Theralase and think about Medtronic's story.
It all has to start somwhere.
So let's look a tale of a couple electrical engineers.
https://wwwp.medtronic.com/newsroom/content/1281109242470.pdf
https://www.medtronic.com/covidien/en-us/products/electrosurgical-hardware.html
The story of Medtronic is one of men and women who have dedicated their lives and careers to helping real people overcome pain and disability to lead more normal, happy lives. It’s a story I never tire of hearing or telling.
— Medtronic co-founder Earl Bakken
MEDTRONIC
Bringing Electricity to Life
Over the past 60 years, we’ve transformed Medtronic from a tiny electrical repair shop in a Minneapolis garage to the world’s leading medical technology company serving customers in more than 120 countries.
Channeling a Passion
When Medtronic co-founder Earl Bakken was an electrical engineering graduate student at the University of Minnesota, he spent much of his spare time at nearby University and Northwestern Hospitals. He served as an eager volunteer handyman, repairing malfunctioning medical equipment so he could learn how it worked.
When Earl mentioned this to his brother-in-law, the enterprising Palmer Hermundslie recognized a business opportunity. So, in 1949, the two started
a repair company focused on medical electronics, and called it Medtronic. Their office was the Hermundslies’ 600-square-foot garage in northeast Minneapolis, Minnesota
Historic Partnership
In addition to repairing medical equipment, Earl also built custom equipment for clients, including Dr. C. Walton Lillihei, a pioneering open-heart surgeon at the University of Minnesota Hospitals. Dr. Lillihei often treated infants with congenital heart defects, and used a pacemaker after surgery while the heart healed. At that time, pacemakers were bulky, AC-powered boxes that had to be wheeled on carts and plugged into outlets. One night, an electrical storm caused a power outage and one of Dr. Lillihei’s pediatric heart patients died. Despondent, the surgeon turned to Earl for a battery-powered alternative. Within four weeks, he delivered the world’s first battery-operated external cardiac pacemaker.
Financial Growth
Medtronic’s first monthly gross was a mere $8 for repairing a centrifuge. By 1960, annual sales were $180,000, and two years later they reached $500,000. The profit picture, however, wasn’t as promising. The combination of a new facility, increased marketing expenses, and significant research investment resulted in a $44,000 loss in 1962. On the edge of bankruptcy, we battled back by obtaining a $100,000 bank installment promissory note, attracting money from a venture capitalist, and trimming staff. By 1963, the company was back on track financially and reported a $73,000 profit on revenues of $985,000. That year, we sold an average 100 pacemakers per month, with about 20% of total sales coming from foreign markets.
Technology Evolution
This innovative pacemaker was called a “miracle,” and orders started coming in from around theworld. While it was a significant breakthrough for treating short-term heart rate irregularities, the pacemaker’s limited battery life constrained its uses. Physicians began requesting a more longterm, implantable pacemaker for patients with permanent cardiac conditions. So we developed a rudimentary semi-implantable pacemaker in 1959, but the battery still had to be replaced almost monthly, so we continued to work on a better solution.
The first successful U.S. attempt at designing a totally implantable pacemaker was reported by the New York team of Drs. William Chardack and Andrew Gage, and engineer Wilson Greatbatch. Medtronic’s founders contacted them about a partnership, and soon we had exclusive rights to produce and market the Chardack-Greatbatch implantable pacemaker. By the end of that year, 1960, we had 50 orders for the device and were now considered the experts in cardiac electrical stimulation.
Sales steadily grew, but the cost of the device, $300 to $500, was prohibitive for many patients. A real breakthrough for sales was passage of Medicare legislation in 1965, which covered the cost of a pacemaker for elderly patients.
Transferring Expertise Into New Areas
During this era, we developed several heart-related products, including a heart monitor and a generator that controlled bleeding during surgery. We also began transferring our electrical stimulation expertise to treat other conditions. In partnership with Case Western Reserve University, Medtronic tested stimulation of the spinal cord to suppress pain. By the end of the 1960s, we also were exploring the use of electrical stimulation to treat varicose veins and gastrointestinal conditions.
Global Expansion
From a Minneapolis garage, Medtronic expanded into a second garage and then an apartment. By 1961, we moved to an official 15,000-square-foot headquarters in
St. Anthony Village in Minneapolis. It was expanded five-fold within a decade, including adding a state-ofthe-art clean room for assembling implantables.
1949 Two Employees, $8.00 revenue
1960 25 employees, 180,000 revenue
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Theralase is up to 24 employees now and inflation adjusted revenue, we're on par so far! :)
Medtronic was a drug delivery pioneer (synchromed).
Theralase perhaps the next generation drug delivery pioneer via PDT/ACT/TLC3000 Series technology and patents.
Medtronic took over the medical device category.
Theralase perhaps can displace platinum group cancer therapies, ALA-5/Photofrin PDT treatments, intraoperative tech/systems/devices/procedures.
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THERALASE
Cancer Cure at the Speed of Light
Borrowed from Robert: https://www.321gold.com/editorials/moriarty/moriarty030314.html
The company is named Theralase Technology. (TLT-V) It is the lovechild of Roger White, company President and CEO. His mother was a former nurse and his grandfather was a doctor. Roger’s father was a watchmaker and jack-of-all-trades
White started working for him when he was 7, learning clock repair and watchmaking. When White was 10 he took apart his own bike just to see how it was made. He was quite good at disassembling the bicycle but when it came time to putting it back together, he wasn’t so good. But as is so often the case in life, he learned a lot more from his mistakes than from his success.
Torn between the engineering side of his father and the medical side of his mother, Roger White graduated as an Electrical Engineer in 1986. But in 1993, his father called him to tell him about an interesting technology he had discovered while on travels in Belgium. It was an “invisible laser” that could double the speed of healing and decrease the pain of injuries.
Roger White traveled to Brussels to meet the inventor of this laser light. The man who invented the specific frequency of laser light explained that the building blocks of connective tissue, fibroblasts, have a 100% increase in cell division when exposed to this particular light. This cuts healing time in half and reduces pain without the use of medicine or surgery.
White fell in love with the concept and bought the rights to the technology in 1994 after meeting with physicians and scientists familiar with the process. He formed his own company to research the product and began manufacturing it in 1995. By 2000 he launched his first medical device product, the TLC-1000. 1200 of these units are in the field and are providing cash flow to the company today.
Theralase is the perfect company for a public financing. We forget that the real purpose of a company selling stock is for it to be able to grow at a faster rate than just by internal financing. A big investor heard of the company and convinced them to accept a big financing. That financing took place in November (2014) and added over $3 million to the company’s coffers.
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If Theralase’s cold laser device was the only dog in the hunt frankly I wouldn’t be all that interested in working with them. They are doing a couple of million a year in sales now. The updated machine due out in September of 2014 combined with the new leasing scheme will triple their revenue. Ho, hum. But then Roger mentioned their cure for cancer. . .
That woke me up. I had to have him explain it to me carefully so I understood it. A cure for cancer without surgery or expensive medicine would be a game changer. Curing cancer at the speed of light would be a world class, perhaps universe class game changer.
In the late 1990s, Roger White read a short piece in an industry publication named Laser Focus World talking about a chemistry professor at a Virginia university who was working on molecules called Photo Dynamic Compounds (PDC) that were attracted to cancer cells. When activated by light, these compounds kill the cancer cells with no damage to healthy tissue surrounding the cancer.
White got in touch with the professor and bought the rights to the technology. Compared to the current standards of care for cancer patients using surgery, chemo or radiation, a simple and safe cure would be a revolutionary product.
Let’s talk about cancer for a minute so you understand how these PDCs work. Normal cells grow and eventually normal cells die. Cancer cells don’t die. They keep growing until they kill the host. There is literally a switch in the DNA of cancer cells that stays on when it should go off.
When the PDC is injected into the cancerous area of the body, healthy cells reject the PDC. Cancerous cells attract the PDC and it combines with the DNA of the cancer cell. When the cold laser light is activated on both healthy and cancerous cells, the healthy cells are not affected and the cancer cells die.
Naturally this process requires a lot of testing. The first test the company conducted is called a toxicity test. The test should measure both dark toxicity and light toxicity. With the PDC injected in the cancer area, the PDC should have no toxicity on any cells because it’s dark. When exposed to light, the PDC on the cancer cells should react. Best case is zero dark toxicity and 100% light toxicity. Theralase found this result in the lab studies of four of their patented PDCs.
The next test Theralase conducted was on a mouse. The company injected cancer cells into a mouse and successfully created a tumor in the mouse. Then they injected their patented PDC and activated it with a laser. This test showed a total eradication of the tumor and the mouse lived an additional 20 months, which is a normal mouse life span. Much to the surprise of the company, the PDC/Laser light treatment also took five strokes off the mouse’s golf game.
The treatment works on a variety of cancer cells including breast, colon, bladder and brain cancer. But Theralase had to pick one specific cancer to work on to get approval of the FDA and Health Canada for use in treatment.
Theralase chose bladder cancer. In the US there are 70,000 new cases yearly and 14,000 deaths from the disease. Spending on bladder cancer amounts to $3.9 billion yearly. There have been no new drugs to treat bladder cancer since 1998. Bladder cancer is the most expensive cancer to treat and has an 80% recurrence rate.
Theralase is in the process of completing a mouse model on dose toxicity, working on the Good Medical Procedures (GMP) manufacturing standards, and finishing the FDA Investigational New Drug application. The next phase will be achieving Breakthrough Status and partnering with a major pharmaceutical company.
Theralase will design the laser. They are ISO-13485 certified and have some 20 years experience with laser devices. Manufacture of the PDC will go out to a GMP facility. At this time there appears to be little regulatory risk. Since the PDC never enters the blood stream it has virtually zero toxicity. The FDA likes new cancer drugs and should love this procedure. Theralase's applications have been fast tracked through the approval process.
This may be the most important company I have or ever will write about. This isn’t just a treatment for cancer; it’s a cure for cancer through what should be a medically benign method. The anticipated cash flow for the next three years from the already tested and sold cold laser devices would more than justify today’s share price but it’s simply not possible to anticipate the financial value for a cure of any form of cancer. It should cure bladder cancer; it may cure breast cancer and even lung cancer. The blue sky on this stock goes from Canada all the way to the moon.
And I really like talking to Roger White. Most of the people I talk to are figuring out in their minds what not to tell me. I know when I am talking to them that I am getting the part of the story they want me to know but I have to pry to find out what I really need to know. Roger’s story of having been a tool and die maker that morphed into president of a cancer cure company fascinated me. I asked him to tell me the story. It’s not something that you would find in a company brochure or on their website or written about by your typical financial writer but it was riveting.
He sat down and immediately wrote me an 1800-word missive that answered all my questions. This piece isn’t very much longer than that and I’ve worked on it for days. He’s not hiding anything. This is the real deal.
To the extent that I believe this is a game changer, I’m proud to be able to write this piece. This company could improve the lives of thousands or millions of people. I hope they succeed. I hope they make a giant fortune, I hope everyone who invests in them makes a giant fortune and I’m triple-thrilled to have them as a sponsor.
I don’t own shares; I’d like my contribution to their success to be doing a good job of telling the story. I f**king love this company.
I will not put in my typical mealy-mouth disclaimer required by the SEC on this write-up. Shut up and buy the stock if you can afford some. If they somehow manage to fail you have contributed more to the health of your fellow man and perhaps even yourself than any other stock I can think of. When they succeed, you have not only done good, you have done well.
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Anyway, I'm not saying TLT is the next Medtronic. I'm saying it could be, it is not likely but it is not impossible. If one electrical engineer can change the world, so can another.
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On September 9, 2011, Theralase entered into an exclusive worldwide licensing agreement with Dr. Sherri McFarland, a chemistry professor at Acadia University, granting Theralase any and all rights to all allowed claims in intellectual property of Invention Disclosure dated July 22, 2011 and all intellectual property rights related to or arising from subsequent improvements by the parties during the currency of the agreement in cancer related therapies and in general, utilizing PDT for the following applications: medical, sterilization, cosmetic, bacteria, virus , cancer related therapies or PDT. Medical or sterilization related applications; include, but are not limited to: research and development of the destruction of biological tissue, especially hyperproliferating cells, such as cancer and destruction of microbial entities, such as bacteria. The license will expire twenty years following the expiry of the last patent, including improvements. Based on the latest expiry date of the Company’s existing patents, the license is expected to continue in effect until April 15, 2053.
Roger 2014: Roger Dumoulin-White, President and CEO of Theralase stated that, “Validation and optimization of our PDC technology is required in order to provide the scientific rigour required to advance this technology to human clinical trials. I am delighted that our scientific and preclinical research teams continue to further understand and validate this effect to allow us to prepare for clinical validation in human patients. If we are able to validate the effect in humans, then the implications of this discovery are nothing short of game changing for both Theralase and more importantly for cancer patients.”
Lilge in 2013 said the following:
At the conclusion of this project a complete suite serving these approved therapeutic modalities will be developed, offering an increase in efficacy while providing the treating physician accurate real-time feedback predicting the clinical outcome.
The Industrial R&D activities supported range from
RF coil ablation for breast (CR Bard),
bone and spine (Benvenue Medical) tumor ablation , (Benvenue Medical)
improving precision in therapeutic deliveries,
photosensitizer development (Theralase),
high-power PDT and laser thermal light delivery systems (Illumacell),
energy distribution and preprocedural planning (Medtronic)
as well as hardware-based pentaflop omputational services (IBM Canada).
A single treatment planning software solution will reduce the individual partner’s burden to reach market approval and transform the attainable the therapeutic ratio for their respective therapies.
Where are we now?:
combining cannabinoids with Theralase’s PDT technology anti-cancer vaccine, RuVaCare, in the destruction of human cancers. (Theralase),
improving precision in therapeutic deliveries, (Theralase)
photosensitizer development tld1433, tld1633, tld1822, tld1829, tld1824 (Theralase),
Theralase has spent the last 17 years developing PDCs, which are light activated anti-cancer drugs. From a portfolio of thousands, Theralase has chosen four lead PDCs, which the company is currently trialing for use in the treatment of bladder cancer.
TLD1633 treatment to be 668,000x more effective than ALA treatment and 198x more effective than Photofrin, both of which are current, FDA approved photo dynamic treatments (PDTs).
TLD-1633, has recently been shown to be approximately 15% more effective than TLD-1433 in the destruction of a human Glioblastoma Multiforme ("GBM") cell line (U87), a deadly form of brain cancer.
In preclinical research, TLD-1633 has also demonstrated a lower dark toxicity, supporting an even higher safety profile than TLD-1433.
Sherri McFarland, Ph.D., Professor, Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, stated that, "TLD-1633 is a natural progression of the research work completed by our research labs in the development of TLD-1433. TLD-1633 has shown even stronger safety and efficacy in our labs than TLD-1433, and I am delighted to work with Theralase to optimize and expand their licenced PDC program as we embark on additional cancer indications."
Arkady Mandel, MD, Ph.D., D.Sc., Chief Scientific Officer of Theralase, stated that, "I am delighted that TLD-1633 has been added to our growing list of compounds, identified by Dr. McFarland's research program, in conjunction with our own, as potent anti-cancer agents. TLD-1433 was originally chosen as the lead anti-cancer PDC in our fight against Non-Muscle Invasive Bladder Cancer ("NMIBC"), because of its strong characteristics, but it seems an even more potent PDC, TLD-1633, may be better suited to be utilized for other cancers of the body, such as GBM, especially when combined with transferrin. This is truly ground-breaking research that myself and the entire Theralase research team are delighted to be involved with."
Theralase is in the process of developing two separate clinical treatment paths for patients who have been diagnosed with GBM to safely and effectively destroy the tumour with minimal side effects.
In the first phase of the GBM clinical study, the participant will receive primary treatment, such as surgical debridement, temozolomide (an oral chemotherapy drug) and/or radiation therapy. They will then receive the vaccine created from the patient’s own tumour cells to stimulate the body’s immune system to destroy residual GBM cancer cells.
During the second phase, the participant will receive an intravenous injection of Rutherrin, a patented PDC (TLD-1433) drug formulation combined with transferrin, to then activate it via laser light somewhere between 8 to 24 hours after injection. This time is necessary to allow the drug to cross the blood-brain barrier and be absorbed into the cancer cells.
Historic Partnerships
One of the greatest implications of this work is that it serves as an example of the remarkable progress that can be made when academic and industrial groups collaborate in an underexplored area. The combination of the chemical and photophysical expertise, provided by McFarland, the medical biophysics expertise of Lilge, along with the clinical light-based medical devices developed by the scientists at Theralase Inc. has resulted in one compound in the clinic and more in the pipeline. It also serves as reminder that conventional wisdom can be misleading, and that there is no replacement for chemical intuition and experimental evaluation.
--cancer vaccines
--combination therapies
--Making cancer technology more precise
--t-cell and cannabinoid molecular tactical aids
--dose and delivery accuracy and effectiveness
-Theralase PDC demonstrated effective Photo Dynamic Inactivation (“PDI”) of bacteria and may prove to be an effective methodology in the destruction of nosocomial (hospital acquired) infections and infected wound sepsis (bacterial infection in tissue).
-The Theralase PDCs have been shown to be highly effective (99.999999%) against numerous species of bacteria, including: Staphylococcus aureus, Methicillin Resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Vancomycin Resistant Enterococcus (VRE), and Listeria monocytogenes (Listeria).
-There are billion dollar markets everywhere that could open up on the bacteria side in industry; hostpital, food - industrial sanitation/atp swabbing/detection, mrsa, ablation hardware.
https://theralase.com/wp-content/uploads/2016/06/V.TLT_Zacks_Q12016_Update.pdf
Research to Combat Bacteria and Food Contamination In the U.S. alone, more than 99,000 people die each year from bacterial infections. While this cost on human life is
high, the financial toll is equally staggering. The World Health Organization ( WHO ) has called healthcare associated infections one of the largest causes of avoidable harm and unnecessary deaths in the developed world.
The Centers for Disease Control and Prevention estimate such infections add an additional $35 to $45 billion in costs to the U.S. healthcare system annually.
Bacterial infection, ranging from superficial skin infections to severe invasive diseases, is recognized as a very serious health threat, representing a major cause of mortality and adding financial burden to already-stretched health care systems. PDCs have been proven to target and destroy bacteria associated with the contamination of
food. Photodynamic Inactivation ( PDI ) of pathogenic bacteria is a unique approach that combines a photosensitizing drug ( PS ) and light to generate cytotoxic singlet oxygen and other reactive oxygen species ( ROS ). This oxidative burst leads to nonspecific damage with multi-faceted targets, including the cytoplasmic
membrane, intracellular proteins and DNA. In April 2012, Theralase presented new scientific data supporting the application of Theralase s advanced
sterilization platform technology that kills 99.99% of life threatening infectious microorganisms, such as Staphylococcus aureus ( S. aureus ). This organism is responsible for both Hospital Acquired Infections ( HAI ) and Community Acquired Infections ( CAI ) that range from relatively minor skin and soft tissue infections to
life threatening systemic infections.
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(TLD-1433 + transferrin) injected IntraVenously into a patient diagnosed with GBM
-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
Have a single low dose of X-ray (1 Gy, 75 keV) and then activate a ru(ii) photosensizer by Near Infrared (“NIR”) laser light (808 nm, 200 J/cm2), four hours after injection.
Stable under X-ray activation and remains able to produce ROS via subsequent NIR laser light activation
Able to be activated by X-ray eliciting a PDT-like cell kill
Able to be dually activated (X-ray followed by NIR laser) delivering a cell kill greater than the two wavelengths applied separately
Able to destroy cancer cells predominantly via necrosis at 24 hours post treatment.
Able to deliver noticeable damage to tumors when X-ray activated
Able to deliver significant tumour damage when dually activated (X-ray followed by NIR laser) in the presence of transferrin
https://hal.archives-ouvertes.fr/hal-01626728/document
The majority of the currently approved PSs are based on a tetrapyrrolic scaffold (i.e.porphyrin, chlorine). However, these compounds have several drawbacks, namely 1) poor water solubility; 2) tedious synthesis; 3) absorption
Of note, the introduction of Ru(II) moieties to porphyrins like in 5 can improve the PDT characteristics (water-solubility, cellular uptake, 2PA-properties) compared to the porphyrin itself. Importantly in the context of this Account, the compound of McFarland et al. TLD-1433
Currently approved PSs are excited in the spectral range from 375-763 nm. 2,9,10 Due to absorption and light scattering effects of the biological tissue, the light penetration depth into the tissue is low at these wavelengths As a result, these PSs cannot be used to treat deep tumors.
the group of McFarland systematically investigated Ru(II) complexes with attached aromatic chromophores that possess low lying triplet intra-ligand (3 IL) states for PDT. With these so-called dyads, compared to [Ru(bpy)3] 2+ extremely long triplet state lifetimes up to hundreds of microseconds could be reached.38 These long lived 3 IL states of dyad PS like TLD1433 are highly photosensitizing. This allows for excitation and 1O2 generation in the biological optical window although only weak absorption!!
high-power PDT and laser thermal light delivery systems (Theralase),
energy distribution and preprocedural planning (Theralase)
Photodynamic Therapy (PDT) is a highly efficacious and cost effectiveness treatment for superficial tumours and enables a fast recovery. However, PDT's efficacy is reduced for interstitial cancers as it is difficult to predict the activated dose throughout the target. Dosimetry is complicated by population variations in the light-tissue interaction properties and variations in the photosensitizer uptake in the target, partially driven by vascular volume and flow, and molecular oxygen supply.
We propose that personalized PDT treatment planning, based on a complete, integrated and robust workflow, will overcome these limitations. The flow will use medical images to assess the extent of the clinical target volume (CTV), its vascular flow and that of organs at risk. We will perform detailed photon propagation and pharmacokinetic modeling to simulate the PDT dose. Our workflow will simulate the outcome for a given light source placement; it will be capable of autonomously identifying the optimized placement of light sources and the preferred sites for monitoring light dose to validate the predictions.
We will create new tools to form an integrated tissue contouring, mesh generation, photon propagation and photon-fluence visualization flow. The physical extent of the target volume will be used to optimize the source positioning to achieve the required photon density in the CTV while minimizing it in adjacent tissues. The required research activities include semi-automatic volume meshing, algorithms for assisted or fully automated source placement, prediction of suitable positions for quantitative optical property extraction and visualization tools presenting the anticipated outcome to the physician. Hardware acceleration using our IT partners' platforms for compute intensive steps such as photon propagation and multi-dimensional dose presentations will be required. The photon-fluence planning tool outputs the spatial locations most sensitive to an individual’s actual tissue optical properties.
To further refine the PDT-dose prediction algorithms, the local photosensitizer uptake and partial oxygen will be modeled based on MRI-derived blood flow and blood volume data for three key photosensitizers, those from our pharmaceutical partners and an approved sensitizer. To accomplish this, we will develop the algorithms correlating blood flow and volume with photosensitizer accumulation for a range of tumours of the brain, head and neck, lung, esophagus and bladder. These calculations will require the use of preclinical studies, validated with ex vivo fluorescence imaging of the photosensitizer and oxygen radical reporter molecules.
Building on our expertise in preclinical PDT and our FullMonte photon propagation simulation package, we will provide an integrated, validated and robust personalized cancer treatment planning tool that will increase therapeutic efficacy and patient safety, allowing our industry partner and physicians to test novel approaches for therapy delivery and novel indications in silico prior to first use in patient
as well as hardware-based pentaflop omputational services (IBM Canada).
See:
https://stockhouse.com/companies/bullboard/v.tlt/theralase-technologies-inc?postid=29677286
https://www.oce-ontario.org/docs/default-source/Presentations/6-vaughn---soscip_oce_forum.pdf?sfvrsn=2&sfvrsn=2
https://www.eecg.utoronto.ca/~vaughn/papers/cascon2016_pdt.pptx
https://stockhouse.com/companies/bullboard/v.tlt/theralase-technologies-inc?postid=29671633
Simpler and faster than setting up our own agile cloud
CAPI hardware enables tight CPU-FPGA interaction
Keep hardware pipeline fast & simple, while CPU handles relatively rare complex events
Large (main memory) storage for mesh geometry
10-60s minutes with highly-optimized CPU code!
World’s fastest software simulator for general Monte Carlo simulation of light
Provider of PDT photosensitizers and lasers: better PDT treatment planning -larger market
Evaluate a treatment plan in silico: can tell if PDT plan will lead to a good result before treatment
Automatic optimization: create a better and more robust treatment plan, quickly
1. Make PDT simulation both fast and accurate
2. Leverage fast simulator to enable automatic optimization of plan, and robustness evaluation with tissue variation
3. Develop full flow from MRI data through simulation to visualization
4. Increase PDT efficacy, and broaden applicability to more cancer indications
We are so fortunate to have this advantage... the best scientists and doctors in these fields with government support. There are thousands of companies trying to cure cancer, working with immunotherapies, misc therapies, PDT therapies, you name it. How many have the alignments this small Toronto company has managed to muster... and get to Phase II human clinical trials.
The PDT treatment optimization process can accelerate the training or physicians, currently only available for ophthalmological applications, and thus accelerating the implementation of this therapy in various LMICs clinical centers.
If they can wrap the complexitites of PDT treatment into a reasonably affordable hardware/software/human capital situation that is error proof and effective.
Every insurance company, country health budget, healthcare care provider on the planet will start exploring PDT treatments that are documented to be effective but lacked effective drugs, drug delivery and ease of execution.
While the full piece of that pie may not be ours,, some hardware/service evolutions are possible but certainly the photosensitizer market is ours for the taking.
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The search for alternative drugs to cisplatin, carboplatin and other derivatives is highly needed due to their severe side effects including nephrotoxicity and neurotoxicity. Ruthenium, among other transition metal complexes appears to be a possible candidate for cancer therapy in the near future.
Raab, Lipson and Schwartz, Dwyer all came before Rosenberg.
Cisplatin won - Big pharma won - When will we win?
Cisplatin replacement will be........
drum roll....
TLD1433 or better McFarland magic compound, x-pdt treatment, dual xray and laser, 432hz soothing music, liposomal curcumin and vitatmin C.. or just an old fashion orange and hummus with some chips and smile from a pretty nurse.. sunday afternoon, ball game on the radio... and you get to not suffer, not lose of quality of life, not die.
You get to live.
The stars are aligned imo and they should take their time. Results are imperative. TLT just needs to get the door open. With the exposure and capital that will follow, there are a lot of things this company could do. We haven't even scratched the surface. I think we're in a vacuum here. Things could change very quickly.
Kudos to Theralase and Roger