Brian Crombie - Good evening everyone and welcome to the Brian Crombie Radio Hour on Saga 960. I want to introduce you tonight to an interesting gentleman who's the CEO of his company and a really interesting therapy a potential solution to cancer I want to introduce you if I could to Roger white. He is the president and CEO of a Toronto-based company by the name of Theralase and they've got a cancer solution and they describe it as destroying cancer at the speed of light Theralase cancer therapy in search of medicine's Holy Grail. Mr White welcome to the show sir.
Roger Dumoulin-White - Hey Brian thanks for having me on.
Brian Crombie - So tell me what is your Holy Grail the speed of light uh cancer killer?
Roger Dumoulin-White - Well the technology involves light sensitive molecules that have an affinity to cancer cells so they're attracted to cancer cells they're absorbed by cancer cells preferentially over healthy cells and they're benign until light activated so we instill these into the body. Currently we're doing bladder cancers so it's an intravesical installation they locate and do bladder cancer cells we then light activate them they destroy the cancer cells and leave healthy cells intact.
Brian Crombie - Sorry what is it that's going into the actual cell you're inserting something
Roger Dumoulin-White - It's a study drug so we have a small molecule which is a powder which we mix with water and it forms a solution kind of an orangey red solution. This solution contains the drug and the drug has the affinity for cancer cells and and how do you make sure it goes to the right spot well that's kind of an interesting point of view. It's a mechanism of action so cancer cells have a very high metabolic rate so they have a very high need for iron so there's a glycoprotein in everyone's body that transports molecular iron to every cell in your body okay. If you look at the periodic table there's a transitional eight metal which is iron right below that is ruthenium right below that is osmium. The drugs that we produce are ruthenium and osmium based, our lead drug being ruthenium-based. So what happens is the transferring molecule this molecule that's in everybody's body can't tell the difference between molecular iron and our drug so the glycoprotein transferrin it joins with our drug and transports it preferentially to cancer cells so cancer cells have what called transferrin receptors. All cells have transferrin receptors but cancer cells have anywhere from 20 to 100 times more than normal cells. So it's kind of a transport mechanism for our drug and our drug is like a trojan horse so it goes to the transferrin receptor the the cancer cell believes it's iron so it freely accepts it into the membrane of the cell. It goes into the cytoplasm of the cell. it's benign until we light activate when we light activate it it produces a very violent form of oxygen called singlet oxygen or reactive oxygen species and it destroys the cancer cell from the inside out.
Brian Crombie - Fascinating. So our body's own molecules that take iron from wherever they are to fast growing cells will attach to your drug take it through the body straight to the cancer cells that are growing very quickly in our need of iron and I presume that this this ruthenium you said doesn't supply the needed energy to the cancer drug that iron would and so you've got it introduced into that cancer cell and then somehow you activate it with light and that light creates reactive uh oxygen species that then disintegrates the cancer cell.
Roger Dumoulin-White - Well when you activate the ruthenium molecule, which is now inside the cancer cell, so you've got that transport mechanism transferrin and taking it to the cancer cell. However it's inside the cancer cell. When light activates the ruthenium molecule it produces singlet oxygen so oxygen is normally bound O2 we all know that but as single that oxygen it's very reactive it wants to join so it goes around like a wrecking ball trying to destroy everything in its path trying to to bond to something and it forces the cell through apoptosis or natural cell death or what's called immunogenic cell death so it destroys the cancer cell from the inside out. It's a very unique way of destroying cancer.
Brian Crombie - That does sound very unique. Tell me - how does the light impact with the ruthenium to create the singlet oxygen?
Roger Dumoulin-White - The actual small molecule is ruthenium-centered so it's got a ruthenium base and it's got what's called a thiophene chain so what happens is the thiophene chain acts like an antenna so the light activates the antenna - sends it down the chain to the ruthenium molecule and the ruthenium molecule produces singlet oxygen. So that's how it it knocks out this oxygen and because it's held inside the cancer cell what we call spatially and temporarily so spatially it's held inside the cancer cell and it produces singlet oxygen so quickly that the cell can't recover. So it destroys it from the inside out. So it goes through apoptosis. So the membrane would break the internal mechanisms the cytoplasm the nuclei the Golgi apparatus - anything that's inside the cell would then get thrown into the space the interstitial space and it would be absorbed by the immune system and then just naturally ejected from the body through the normal processes.
Brian Crombie - Really fascinating. It's almost like you're throwing a grenade right into the middle of a cancer cell.
Roger Dumoulin-White - That is the way it works. So it's because urothelial cells - we are talking about bladder cancer now - healthy urothelial cells don't have transferrin receptors - or a lot of them. They don't pick up the drug and because healthy cells are able to like the the process for iron molecular iron in a cell takes about 20 minutes. So by the time the transferm receptor gets to the cell, transports the iron inside the cell, and then leaves the cell again it's about 20 minutes. If you're looking at cancer cells that could be anywhere from eight hours to 72 hours so they are very very slow at releasing the iron or releasing the ruthenium in this case. So all we really have to do is wait over 20 minutes and then the cancer cell retains it the healthy cell does not. We activate it with light and we destroy it.
Brian Crombie - Now how did you come up with this conclusion that light and ruthenium create singular oxyge?
Roger Dumoulin-White - We're not the inventor of the technology. We licensed the technology from a female chemistry professor. Over the life of the company - we've been working on this for about 20 years - we've licensed three different platforms of compounds. So the first platform we brought in from Virginia Polytechnic University in Blacksburg Virginia. So we brought in those compounds. They were really good compounds. They had a lot of energy had some good destruction. They didn't have the best characteristics that we were looking for. We ended up winning an award in Popular Mechanics for one of the top Technologies in the U.S I think in 2010 and we got contacted by another female chemistry professor and she had two platforms of technology. So a ruthenium-based and an osmium based - we ended up licensing both of those platforms as well and we started to develop those technologies and they concern or they encompass thousands and thousands if not millions of different variations of these compounds. But through drug discovery we found one very particular one we call TLD1433 and we've now given it a brand name called Ruvidar. That technology had a lot of promise. Really really good characteristics - things that we're looking for. You're looking for something that has a high affinity for cancer cells, that can bind with transferrin, that has a very high singlet oxygen yield, it's activatable in the visible red or the visible wavelength and also the red wavelength - a number of different features - it's easily dissolvable into water. So these are all characteristics that we look for and we started developing those with Princess Margaret Cancer Center out of University Health Network out of Toronto. We went through dark drug discovery, we went through in vitro which is cell work, small animal in vivo work which is small animal work. We went through toxicology. We went through a phase one clinical study and now we're in the middle of the phase two clinical study - about halfway through which is a pivotal phase two clinical study. If we're successful we'll end up getting marketing approval or commercial rights in Canada and the U.S
Brian Crombie - You know, most people think that drug discovery takes a fair amount of time and a fair amount of money give me a sense if you could of how long this process has taken will take and how much are you investing in it
Roger Dumoulin-White - The rule of thumb for drug discovery from concept through to commercialization is typically 15 years and the cost to big pharma's about 1.4 billion dollars U.S. We've been on this path for this particular set of compounds since 2011. So it's been about 12 years it will take us another two or three years to finish the phase two - go through all the trials - get all the data in - deal with data lock - get in front of Health Canada and the FDA. So the 15-year mark seems about right. As far as investment, we're not at the 1.4 billion U.S. We'll probably end up, I would say, putting about 100 million U.S Canadian into the project. So about one tenth the average, much much lower. We don't have the big overhead. I think with big Pharma what they've done over the years is they used to have huge research departments so they used to have you know 70 000 scientists or 50 000 scientists - so this huge overhead and they used to develop their own drugs but what they found is that you know some of them work some of them didn't work. I remember reading a story about a Pharma company that put 900 million U.S into developing a drug and then ended up throwing it away because it didn't deliver on the characteristics they were looking for. So what big Pharma does now is they have a lot of cash they have big tills and they look for winners and losers and they wait for the horse to cross the finish line and then they just buy that horse. So why it's cheaper for us than them is because we're much more focused on a particular molecule and a particular disease versus big Pharma which may be looking at multiple diseases and maybe running multiple clinical studies. For example the monoclonal antibodies are the big ones that they're using now the atizos the pembros the opdivos and these are molecules that they're using for so many different clinical studies that they'll run tens or hundreds of clinical studies at once so that could add a lot to the cost.
Brian Crombie - Now you've been with Theralase for quite a while. I think you and I bumped into each other about 15 years ago or something like that and at the time you were focused on low intensity light lasers. Tell me where that part of your business is.
Roger Dumoulin-White - Well we started out in that business in 2004. That's how I got into the industry where we were developing laser systems for eliminating pain, removing inflammation, accelerating tissue healing. So we're using red and infrared light. We developed that into a multi-million dollar business in Canada in the US who are selling internationally and it was a good little core Business but I read a an article I think this was in probably late 1999 early 2000 about this female chemistry professor that was developing these compounds for cancer that were light activated. I became very interested in it and I wrote to her she sent me a research I couldn't understand any of it. It was so complicated with chemical names 15 inches long and I became very interested in this technology and I thought it had a lot of merit so we continued running the therapeutic laser business and we still do today. It's still part of our core business but we took a lot of time in our effort in developing these anti-cancer Technologies. We feel that that is the way forward. You're looking at subsets of patients and disease states that don't have any good outcome measures like there are developments happening but the standard of care has traditionally been surgery and chemotherapy, radiation you know these have a lot of side effects. They're very hard on a patient's body. They destroy a lot of healthy cells. So we became very interested in technology that would be able to destroy cancer cells but leave healthy cells untapped and be able to destroy the disease for the patient.
Brian Crombie - Your experience with light - with the low intensity light laser must have helped you with this cancer treatment and the light activation of the drug is that true?
Roger Dumoulin-White - It allowed us to pivot because the knowing that technology and building laser systems we're able to build a laser system so the drugs are in license so we in-license the drugs we have them manufactured at GMP facilities or good manufacturing practices facilities in Canada and the U.S. The lasers are all developed by us so all the laser systems, the fiber optics are all developed with our team of engineers.
Brian Crombie - You're a public company?
Roger Dumoulin-White - I am or we are. The ticker is tsxv on the Venture exchange - TLT on tsxv so tickers TLT We're OTC as well QB we're TLTFF
Brian Crombie - Excellent. And you're at 35 cents and about 70 million dollars in market cap is that correct?
Roger Dumoulin-White - I think we're a little lower than that. I think we're about 26 and a half cents Canadian and probably a 57 million market cap.
Brian Crombie - Okay your your website is a little bit of date then.
Roger Dumoulin-White - I apologize. It probably is out of date. Yeah, I think the current trade we're a little lower than tha.
Brian Crombie - Okay and obviously you can't talk a lot about your prospects but obviously you're positive on this drug and the impact on your share price.
Roger Dumoulin-White - Well I think that the technology has a lot of merit. Our latest clinical study results that came out May 30th hows some impressive results. So the FDA put out guidance in 2018 on a very specific subset of non-muscle invasive bladder cancer which they call BCG unresponsive non-mustle invasive bladder cancer carcinoma in situ. So the standard of care is a bacteria that was originally developed for tuberculosis called bacillus calmette guerin so they used a watered-down version of that which they intraversically inject in your bladder and it has a lot of results. So in non-muscle invasive bladder cancer 75 percent of the patients respond 25 don't. Sothey're considered BCG unresponsive. The problem with BCG is - A - it's in short supply in the world and the recurrence rate's about 50 percent at 12 months. So although 75 percent would respond positively half of those patients recur again at one year. It just comes back - it recurs. So the FDA put out guidance in 2018 saying well what do we do about this population of BCG unresponsive nmibc and they said you know let's make it tougher. We're only going to go to high grade disease which is called carcinoma in situ, not papillary disease, which would be on the inside of the bladder but it's kind of like a red shag carpet on the inside of the bladder so they made it very very tough - a very very small subset. But they said these patients don't have a lot of options. If they fail BCG they're going for radical cystectomy which is a removal of the bladder - removal of various female and male genitals - removal of lymph nodes. It's a very intense surgery. So it has a high morbidity, high mortality rate. So they said - what do we do with this population? So they put this challenge out to industry. Theralase is one of the companies that addressed it. So we came up with this drug and this device in order to destroy it. So they were looking at the international bladder community who said well if you could get a response in half of those patients - you could give them a complete response at any point in time and then you could keep that for half of that amount or 25 of the original population at one year, that would be a huge win. We would have something that would be widely adopted across the medical community internationally. There's a drug called vicinium which was approved by the FDA, I think 15 years ag,o and it had a kind of a dismal response at 12 months. I think it was about seven to ten percent complete response rate. So only one in ten patients would be able to have a complete response. The second drug that got approved was by Merck - their Keytruda drug. And it got approved in January 2020 and it had a 41 percent complete response rate at any point in time but at one year was around 19 percent. So a little low but they still got approval. The latest data that Theralase has put out - we had a 66 complete response rate at any point in time with 33 at 15 months. So dramatically higher than what's already been approved. So we think it bodes well for the future of the company. And it bodes well for value of the organization. Hopefully it bodes well for the shareholders and the stakeholders in the company as well.
Brian Crombie - And was this in your phase 1?
Roger Dumoulin-White - We're in the middle of a registration trial - phase two halfway through.
Brian Crombie - So these results that you published were from your phase two trial?
Roger Dumoulin-White - That's correct.
Brian Crombie - So how many people are enrolled in your phase 2?
Roger Dumoulin-White - We're looking to treat 100 to 125 patients. We've treated almost 60 - 59 to date - so we're looking to wrap up that study end of this year beginning of next year. With the last patient in we'd have to wait 15 months to follow them up because that's the study design. So we'd be looking to have a complete data set in about 15 - or about first, second quarter of 2025 and then from there we'd be looking at either a six or ten month approval depending on whether the company was able to achieve priority review with the FDA. So in 2025 beginning of 2026.
Brian Crombie - You would only need a phase two you wouldn't need a phase three?
Roger Dumoulin-White - No - because of the guidelines that the FDA put out with this you can compare your active arm to historical standards, so for this patient population, because they have no other options, it would be unethical for example to not give them the drug and not light activate it. So the medical community and the FDA and Health Canada agrees that you could go across in a historical standard so in a phase two the FDA again in their guidelines - if you're running an intravesical instillation so you're putting the drug in through the urethra into the bladder you can go and use a single arm study. You don't have to go to a phase three. You don't have to go to a double arm study. It could be an open study.
Brian Crombie - That's interesting. We need to take a break for some messages and will come back in just two minutes. We're with Roger white, talking about Theralase, the company and his Holy Grail of a potential light activated drug therapy to destroy bladder cancer. Stay with us everyone we'll be back in two minutes..... welcome back everyone to the Brian Crombie Radio Hour on second and 60 Busch Avenue - tonight with Roger white. He is the president and CEO of Theralase. They've got an anti-cancer therapy that targets and destroys cancer cells and they're looking right now at bladder cancer and it's really quite interesting because what they do is they inject into you, I guess through the urethra, a drug that is a powder mixed with a liquid and then it's injected into the body and it is with rutherrin which is like iron and there's proteins - there's molecules in our body that carry iron and will also carry ruthenium to cells that are in need of iron - cancer cells that are in need of a lot amount of iron and so therefore there's a natural mechanism that takes this drug from where it's injected into our body to those cancer cells. And then once it's there in those cancer cells it goes into those cancer cells and and Roger and Theralase shine light on it and the light activates the drug. The drug turns into radical oxygen species singleton oxygen and that destroys the cancer cells. So it's like putting a grenade into the middle of the cancer cells and blowing them up. Absolutely fascinating. He's gone through a phase one. He's in the middle of a phase two clinical trial. He thinks he's going to get results by I think you said 2025 and and so therefore you might get approval thereafter. You're going to spend about 100 million dollars about one 12th of the 1.2 that typical big Pharma spend and while you're at that 15-year sort of time frame - if you actually get approval in 2025 and not have to do a phase three in totality particularly from today it's a lot shorter than what a lot of drug candidates go through. So that's great. Now tell me about your phase two. You're about halfway through - maybe a little bit above halfway through your recruitment why is it taking so long to recruit all your patients? Is it a very rare cancer - that difficult to find patients that will enter the trial?
Roger Dumoulin-White - It is. When you're dealing with - first if you look at Canada - we'll talk about Canada - there's about 13,300 new bladder patients every year about 75 of them are non-muscle invasive bladder cancer. So 25 are muscle invasive. So the disease has gone into the detrusor muscle. Those patients are scheduled for radical cystectomies or having their bladder removed. Of the remainder, the 75% of the Thirteen thousand there's only about five percent of those which are carcinoma in situ. So you're getting into smaller and smaller numbers and when you look at that, those patients are spread all across Canada. So they're not in one location or in Toronto or Vancouver or wherever. They may be so it's a very unique subset. So the reason that the trial takes a long time is in Canada in the U.S it's a very unique patient population or it's an orphan subset of non-muscle invasive bladder cancer patients that don't know about our study. There's also competitive studies. So there's other studies run by big Pharma that are using other therapies - monoclonal antibodies etc. So it's hard to enroll in the study. So it does take quite a bit of time. We started it in August 2019. We were going really really well. We had enrolled I think about 12 patients up until March 2020 and then this wonderful thing came along called the global Covid-19 pandemic and shut everything down and shut the clinical study sites down the hospitals everybody. Attention turned to this new virus so that slowed down our process. Things started picking up again in late 2020. In the middle of 2021 things became a little bit more normal - I think at the end of 2022 into 2023. So things have slowed down. So it's a very select patient population and we had almost three years of a pandemic slow us down.
Brian Crombie - You've got about a 50 million market cap today you say approximately. If you were approved what what would be your potential revenue?
Roger Dumoulin-White - Well the market size - I don't know what our revenue would be - but the market we're looking at - the addressable market is anywhere from about a billion U.S to around 11 billion U.S per year. So depending on the market, if you're looking at just the US it's probably in the one to one and a half billion range. If you're looking at internationally you know it could be up into the seven to the 11 billion. So there's a lot of data that's coming out saying that bladder cancer is highly linked with smoking. So if you look at the smoking and somebody has a cigarette or whatever their tobacco choice is the body is very efficient at processing that so the nicotine goes to the ? centre in the brain, it gives you that rush which is great but all the nasty chemicals which are in that cigarette smoke get filtered out through the kidney, drop down the ureter into the bladder. These carcinogenic materials sit very close to the bladder wall so they over time can erode that bladder wall destroy the urothelial layer and eventually introduce these carcinogenic materials very close to your bladder cells and make them bladder cancer cells. So what's happening I think in today's world is that there has been a lot of news I've seen in developing countries a lot of other countries for people smoking. There's also been a high prevalence of young female smokers. So bladder cancer has traditionally been a male disease so it's the 10th most common in the world - sixth in men 17th in women. So traditionally it's been associated with men - older men. It's generally an older individual's disease generally happening after the age of 60 but not always in men and I think with the prevalence of female smokers - young female smokers - as this goes on decade after decade I think you're starting to see a higher prevalence of smoking among that population.
Brian Crombie - Do you take this treatment to this drug once or more than once.
Roger Dumoulin-White - This is a one-and-done theory so the the technology it's not like an intravenous drug that you take every two weeks or three weeks - this is a in-office procedure which is done in the operating room. So the patient, for example, let's say they had bladder cancer unfortunately God forbid and they were coming in for this therapy. They would come in at seven o'clock in the morning they would have the drug instilled in their bodies in their bladder at around eight o'clock in the morning they would go into or they would be put under general anesthetic they would have their bladder flushed then they would have a a metal urea cystoscope inserted, which is what the your oncologist uses to see inside the bladder, they would have the bladder filled with water, you would then insert a fiber optic assembly, which is going to do the light activation. So the drug has been instilled in their bladder from eight o'clock to nine o'clock they now go in for the study device section so from nine o'clock to around 10 30 the drug is activated in the bladder and is flushed. They are woken up out of general, they go into the recovery room and they get to go home in the afternoon. So it's a very unique process which is a one day event.
Brian Crombie - Right, And to get approved in Canada you would need to - number one get approval from Health Canada and then get on the provincial formularies to put you on their formulariea in the United States the FDA and then what you need to go to all the managed care and and people who try to get reimbursement is that correct?
Roger Dumoulin-White - Well the first thing I think and you're correct, is to get the regulatory approval so that Health Cannada and the FDA after that. Yes you'd get up on the formulary and you'd have to get on the insurance companies and the providers and look at it. You would have the approval but now you face the the battle of how much are they willing to pay for this?
Brian Crombie - And so that's - how much do you think they would charge? It wouldn't be an issue in Canada if you got the provincial formulary approval how much would you charge in the United States do you think?
Roger Dumoulin-White - It's hard to say but you'd have to look at standard of care. So a lot of the monoclonal antibodies currently they're running about 10 to 15,000 U.S per month. So if you're on that for a year or two years you're running into the hundreds and hundreds of thousands of dollars. I think it's realistic to say that something like this may cost a few hundred thousand dollars in order to deliver this. It depends. You'd have to put it in context with the population, what's currently being charged, the duration of the response etc.
Brian Crombie - That's a hefty figure but I guess if it takes care of cancer it's worth it. This idea that a light activated drug could destroy cancer cells must have applicability beyond bladder.
Roger Dumoulin-White - It does. We are actually developing a intravenous or an IV installation of the drug. We've completed all the work - all the pre-clinical work and we're just going into what's called toxicology analysis. So we have to look at the different levels of the drug and what are the safe levels for human use. Having completed that we plan to start a phase one clinical study for glioblastoma multiform which is a very deadly form of brain cancer and for non-small cell lung cancer.
Brian Crombie - Well good luck this sounds fantastic and I really hope you're successful for benefit of all of us.
Roger Dumoulin-White - Absolutely. For all the patients - that's our primary focus - patient betterment and to deal with a deadly disease and to provide this technology Canadian made.
Brian Crombie - If people are interested in your study and think that they couldn't enroll what's the process? Is there a website they can go to to enroll in the study.
Roger Dumoulin-White - There is. I think the easiest way to go is if you go to our website www.therallaze.com that's a good resource. From there there's also a clinical trials registry called www.clinicaltrials.org and if you look up Theralase you'll be able to see all the clinical study sites which are enrolling and treating patients in our study in Canada. I can tell you it's McGill University out of Montreal, it's University Health Network or Princess Margaret out of Toronto, there's Nova Scotia health authority out of Halifax, Nova Scotia there's London Ontario so the main hospital in London and also Vancouver Coastal Health or the University of British Columbia in Vancouver. So there's five sites in Canada
Brian Crombie - And what about your stock? If you're interested in the stock where can one get investor information?
Roger Dumoulin-White - Contact Theralase.com - you can contact our investor relations department you can reach out to myself or the CFO or the chief scientific officer. So we're actually in the middle of a raise at the moment so if they're interested they can certainly reach out to us.
Brian Crombie - How much are you raising right now?
Roger Dumoulin-White - Up to five million dollars.
Brian Crombie - And have you got a prospectus with the OSC?
Roger Dumoulin-White - No this is a non-broker private placement
Brian Crombie - Okay excellent. Well Roger white it's a pleasure to meet you again and chat with you about your cancer treatment and best of luck because these are the kinds of treatments that we need to have approved and on the market and saving people's lives
Roger Dumoulin-White - That's perfect. I appreciate your time Brian.
Brian Crombie - It was great. That's our show everybody, thanks for joining us. I'm on Monday through Friday at six o'clock on 960 AM. You can stream me online at triple W saga960am.ca Good night everybody