There, Dr. Pete Smith. Hi, Pete.
Hello, everybody. Hello, Jane. Thank you.
Hello, Dr. Daniel Tillett, who's Race Oncology's CEO and Managing Director. Hi, Daniel.
Hi, Jane. Hi, everyone.
Hello. Tonight, we also have a special cameo from Race Oncology's Vice President of Research, Professor Mike Kelso. Evening to you, Mike.
Hi, Jane. Hi, everyone.
Hi. OK, so housekeeping. The format for tonight is that Pete, Daniel, and Mike will run us through a presentation. It's been lodged just now with the ASX. A word of warning, it will contain some science, but it will also contain the so what from a commercial perspective on Race Oncology's announcement regarding significant IP progress this week. After we've made it through the presentation, we'll open up the floor to Q&A. If you'd like to ask a question, you can do so using the Q&A function in the ribbon at the bottom of your screen. We'll get through as many as we can in the time that we have. We've earmarked about an hour for tonight's webinar. With that, I will ask Pete for you to start your screen share and then pass it across to Daniel to get us on the road. Thanks.
Thanks, Jane. Next slide, please, Pete. I'll give you a brief overview and then pass it on to Mike initially and then on to Pete as well. I'll come back for a bit more later on. We really want to just cover a few key points up front. Make sure you sort of take away this. There will be a lot of science. It may get confusing at times. Don't worry about it. If you don't understand, it doesn't matter. What really you need to focus on as an investor is the commercial potential and what this all means. The simple science side of things is that bisantrene was found to consist of three photoisomers. This has been known by us for a while, but it wasn't known by anyone else.
This has enabled us to work out how to keep it in the form that's most active and also how to go about patenting this discovery. We filed three patent applications covering the chemical structure of the isomers, how to make those isomers, how to formulate them, and how to use them most effectively. If these patents are granted, which all the advice we've received to date is that they are likely to be granted, but of course, we all need to know as we work through, we'll have 20 years' composition of matter. This has significant implications not only for our current RC220 formulation, which is in phase one trial at the moment, but also for the original formulation RC110, and Pete will talk more about that later on.
Ultimately, it comes back to what biotech is all about, identifying new IP, developing that IP, proving that out, and generating real value for shareholders. This is a major step in that direction. On that, I'll pass you over to Mike to give you a lesson on chemistry. Thank you.
Thanks a lot, Daniel. I'm going to start off my presentation just with a very quick introduction to some chemistry. Shown on the left-hand side of the screen there is the structure of bisantrene, written in a longhand notation where we show all of the carbon atoms, all the hydrogen atoms, and all of the nitrogen atoms, and all of the bonds that link those atoms together into a scaffold. You can see some of those bonds are single lines and some are double. They're single and double bonds. What that structure represents is the molecule of bisantrene. In fact, the composition of matter patent is what is shown on the screen. That's what gets covered, is that particular architecture of how all those atoms are linked together and how that determines how they function and why bisantrene does what it does.
On the right-hand side is the chemist representation in the form you would have seen on the ASX release. Much simplified. All those hydrogen atoms are missing, but as chemists, we know they're all there because of the properties of the atoms involved. Next slide, thanks. OK, what we're showing here on the left and highlighted in orange there is what we call EE bisantrene. That's the structure that you always see drawn for bisantrene. I'll draw your attention to the red parts that show E next to it. They're the important bonds for this discussion. Those carbon-nitrogen double bonds are called hydrazone bonds. Theoretically, they can exist in two forms, both E or Z. Historically, bisantrene has always been assumed to exist in that EE form shown on the left. What can happen is, or what can potentially happen is I've got a molecular model here.
You can see we've got the three rings of bisantrene shown down the bottom. I've left off the bottom half just so I can hold this model. The important part is this bond shown here where my finger is touching. That's the carbon-nitrogen double bond. It's shown currently in the E configuration. If we move it to the Z, all that means is we're pulling this part of the molecule off and we're reattaching it down here. Now we have a completely different molecule because this group now is very much interacting with this structure down here. When I say theoretically, that can happen, meaning that these bonds can exist in E or Z forms. In reality, most times hydrazones are almost always in this E form. What we're showing here is the theoretical possibilities for bisantrene isomers. Next slide.
All right, I'm going to give you a bit of the history around the discovery here. It all dates back to an early toxicology study the company was doing, which is where you administer the drug to animals and you study the effects of the drug. Part of the study involves taking blood samples from the animals and analyzing those samples using liquid chromatography, mass spectrometry, or LCMS. What you do that for is so that you can understand what the concentration of bisantrene is in the blood at the time at which you take it. When we did this experiment, what we noted was, firstly, some of the samples looked just like we'd expect, where a single peak comes out, shown on this chromatogram, LCMS. That symbolizes that's EE bisantrene. What we also noted was that in many of the samples, this second peak was appearing.
It was appearing in really unpredictable amounts. Sometimes it was quite a lot, like the middle one. Sometimes on the right-hand side, a little bit. Sometimes none at all, like on the left-hand side. One of the other things that we knew about this peak that was appearing is it had the same mass or molecular weight as bisantrene. That immediately tells us it may well be an isomer of bisantrene. What that means is it's got the same number of carbons, hydrogens, and nitrogens in the molecule. Initially, we thought perhaps this is forming in the animals themselves. What we then thought is that's probably not happening because it was so variable, the amount of this new peak that was forming, you couldn't explain it using the principles of metabolism.
That led us to think perhaps there was an explanation here that involved exposure to light, where the samples that were going into the animals, so the infusion solutions, were receiving variable amounts of light exposure prior to going into the animals. Potentially, the samples, when they were coming out of the animals in the blood, those blood samples were being exposed to light to variable amounts before they got analyzed. That was the thinking at the time. We had to go off and do an experiment to try to figure out if that was the case. We did this one here. What this experiment involves is you take a sample of EE bisantrene in water. You just dissolve it up. It's pure EE bisantrene, what you start with. Expose it to light for varying amounts of time and monitor that solution by an analytical technique called HPLC.
When the sample was protected from light, with no light exposure, we see the expected chromatogram, only a single peak, meaning that's EE bisantrene. After 15 minutes of light exposure, which is a very short time, and this is lab light exposure, so ambient light, we can see the appearance of this new second peak. If we have half an hour of light exposure, you can see that now that second peak is as big as the first one, meaning you've effectively got a 50/50 mixture of those two compounds. This experiment made us pretty convinced that it was ambient light exposure of bisantrene, EE bisantrene in solution, forming this second peak. At this point, we didn't know what it was. We had some suspicion that it was an isomer based on the molecular weight.
What you've got to do then is isolate a pure sample of the new peak that's coming out. We did some work and figured out a way to get a pure sample. The chromatogram shown on the left means that's one peak, that's one compound, and that's our unknown second peak. Lo and behold, when we took that sample, even stored in the dark, it re-equilibrated or reformed EE bisantrene really quickly. You can see there's two peaks there showing, indicating that was happening. Eventually, we figured out that we could solve that problem for the purposes of the analysis just by getting the analysis immediately after we purified that peak. We couldn't wait at all. We took that sample to the machine, which is called a nuclear magnetic resonance spectrometer, and we created this thing that's shown on the screen called a spectrum.
What this spectrum shows us, all these peaks that you can see, they correspond to the exact molecular architecture corresponding to EE bisantrene. It was absolutely unambiguous proof that that second peak that was appearing was EE bisantrene. Just to summarize what we're talking about then, we start off with EE bisantrene. Both of these carbon-nitrogen double bonds are in that E form. Visible light is shown onto the solution of those molecules, and then we get this conversion over to EZ bisantrene, the first one shown in the middle. Those arrows that you can see show interconversion. That means that once it gets to EZ, it can actually go back to EE and eventually reaches what we call an equilibrium. You can also see that on the right-hand side, there's a ZZ isomer. We do see this sometimes, very small amounts usually.
It's not really part of the major part of the game that's going on here. It's really about EE and EZ bisantrene. OK, now that we knew what the structure of our mysterious new molecule was, the EZ bisantrene isomer, we wanted to know how active it is as an anticancer compound. The way you would normally do that is you would isolate a pure compound, EZ bisantrene, and test its ability to kill cancer cells. I've already shown you, though, that we couldn't get hold of pure EZ bisantrene easily because it re-equilibrated back to EE. What we thought we could do then is, OK, let's just create varying mixtures of the two isomers and test their anticancer activity. That means their ability to kill cancer cells. We chose this breast cancer cell line, MDA-MB231, to do this experiment. Shown underneath there, you can see zero hours.
That means there's been no light exposure on a sample of EE bisantrene, 100% EE. If we did the 15-minute exposure, 0.25 hours converts it to a 73 to 27 mixture. You can see increasing amounts of light cause increased amounts of EZ bisantrene in the solution. We take those solutions and we treat these MDA-MB231 breast cancer cells with the compounds. We see what they do relative to one another. Shown at the top right-hand side there on the graph, we're plotting cell viability. That's effectively, think about that as the number of cancer cells that are alive in a solution. On the bottom axis, the x-axis, we're showing increase in concentrations of drug or mixtures, in this case, added to those solutions. Following the black line, you can see when the concentration is low, all of the cells are alive.
As you increase the concentration from left to right, you see the curve goes down. You reach a point where 50% of the cells are still alive. That's the point we call the IC50. That tells us how much drug is in solution to cause 50% of the cells to be killed. Of course, you want that number to be really, really low because that tells you that your drug, you don't need a lot of it to kill cancer cells really well. When there's no EZ bisantrene present in the mixture, we see the number there is 265. When we have a bit more EZ, that number goes up to 310. Then when we're starting to get really significant amounts of EZ isomer, 482. Finally, 824 nanomolar, that is the unit of that measurement. That tells you how many molecules are present.
Just down the bottom, this is a plot showing those values again, IC50 for those four different treatments versus the amount of EZ bisantrene present in the solution. You can see, if you follow that line from left to right, that the number goes up and up and up, the IC50, telling you that as you have more EZ bisantrene present, your ability to kill those cancer cells is diminishing greatly. While we couldn't determine whether there was any activity of EZ bisantrene because of its properties of re-equilibrating back to EE, this graph shows us, you can see by the rate at which it's accelerating northwards, that if you got to 100% EZ, you're ultimately going to be finding that that compound has got very little, possibly no anticancer activity.
OK, so that's told us that EZ bisantrene against that one particular breast cancer line is poorly active or low activity. That's only one cell line. We thought, let's try and see what happens across a really broad range of cancer cell lines. We've tested 143 cancer cell lines, representing 23 different tissue types. That's covering things like pancreatic cancer, stomach cancer, lung cancer, skin cancer, all sorts of different cancers. We do effectively the same experiment that you just saw. We measure the IC50 values. We measure it on a pure EE bisantrene solution. You can see 100% EE at the bottom. Another one we've purposely summarized to 58% EE, 42% EZ. We treat each of those 143 cell lines with both of those solutions separately. We measure the IC50.
On the graph shown on the right, if you concentrate on the EE bisantrene column there, each of those dots represents one of those 143 cell lines and its IC50, if you read it off to the left there on the y-axis. The same for the mixture. What's really telling here is the line shown in both of those columns, which represents the average IC50 across that whole cell panel. On the left for EE bisantrene, we see that it is lower than on the right. That tells us again that on average, EZ bisantrene-containing mixtures are less able to kill these cancer cells across the whole panel. OK, so that's some of the experiments we've done. To give you a flavor for how we made this discovery and what we know about it, I'm going to pass it over to Dr. Daniel Tillett now.
He's going to tell us about the patents and the value that they bring to Race Oncology.
Thanks, Mike. This brings us back to this composition of matter IP again. I'll take a little bit of time to explain why this has so much value to the company. Composition of matter claims protect the chemical structure. We've been through, from Mike, quite an extensive description about the actual different chemical structures that bisantrene can form. We now can have claimed we've made this discovery, wasn't known before. We can actually claim that only the EE bisantrene form is active. These are the composition of matter claims. In patents, they're the strongest possible claims you can get in the pharmaceutical industry. They basically protect your drug molecule from any infringement by any generic manufacturer or other manufacturers. People basically can't go out and sell your drug without your permission or licensing it from you.
As a consequence of that, this drives a lot of value for a new drug with composition of matter IP around it. It means that anyone who acquires the patent or purchases or licenses the patent from you doesn't have to worry about someone else competing against you. If you think about the difference between new drugs and how expensive they are, oncology drugs can be easily over $100,000 per patient per year versus a generic drug, which might be $50. You can see there's a huge difference in the value of having a composition of matter. The only thing that protects that $100,000 pricing is composition of matter IP. It prevents generic competition. There's also the potential there of having an additional patent extension that pretty much only applies to composition of matter IP. That gives you, instead of the 20 years, you can have actually 25 years.
That's potentially very valuable as well. You can't work around composition of matter IPs by changing the formulation. You can't just make a new way of packaging up a drug and selling that. This means that you're really stuck, you have to wait till the end of the composition of matter IP. Generic manufacturers always wait till the end of the composition of matter before they introduce a new drug onto the market. You can think about all of this is that the patent life becomes critical to the value of any IP. It's particularly relevant to drug IP because it takes so long to bring a drug to market. Between the original discovery of a new drug, the original chemical discovery in the lab, and by the time it's sold to the first patient, it could be 10, 12, 15 years.
All that time, as a pharmaceutical company, you're spending money developing that, making a loss continuously. You only get to recoup on that investment after a long period of time. The longer that you have to recoup that, the more value there is to the drug. Chris is basically what's called the net present value of the drug. Pete, next slide. People have asked, and I know there's probably a few questions in the seminar, how likely is it that we're going to have a composition of matter patent? Ultimately, the only way to find that out is to submit the patent and wait for the ruling. What's required for a patent? You can get a pretty good idea whether a patent is likely to get through. You can get advice from people skilled in the art of patent writing whether your patent is likely to get up.
You need three things. It needs to be novel. It needs to have utility. It needs to be useful for some purpose. Most importantly, it needs to be non-obvious. It's not non-obvious to an average person, non-obvious to someone who's skilled in the art of the invention. That can be quite difficult. If you have a new chemical matter, it needs to be not obvious to anyone who's a skilled chemist. The discoveries we've made around bisantrene fit all three of those. The novelty, no one knew about the photoisomerization of bisantrene. They certainly didn't know that only the EE form was active. You got some utility there. The non-obviousness, most chemists, as Mike mentioned, would look at the structure and would not think that photoisomerization and stable photoisomerization would be something that would occur.
It's only through careful follow-up of research and really putting effort in that we've been able to get to that point. That really does move it a long way from doing something you would see straight away if you were a skilled chemist. We filed three patents around this discovery, one on the structure and the isomer forms of bisantrene, so all the discovery of the photoisomers. That's the composition of matter patent. We also have ones around administering the patent and keeping it in the form, the right form. We also have around the process of manufacturing pure EE bisantrene at scale, which is not an easy thing to do. There's a lot of complex chemistry and other processes involved in actually ensuring that you get pure EE bisantrene. You don't want to be injecting some sort of crude mixture into a patient.
You want to be injecting a very high-purity drug. That's not a straightforward process. This brings us to these mixtures of isomeric mixtures. Why can't you just go ahead and use the mixture? You could just make up, add a bit more because some of it's converted to EC, and you just increase the dose to the patient. Apart from the fact that, of course, because it's due to exposure to light, you have a problem because some patients will get a small amount and others will get a large amount. It really comes down to the regulatory agencies, the EMA, the FDA, TGA, do not like mixtures of different isomers. These are called isomeric mixtures. These drugs have a real problem. They're very common, particularly for older drugs.
The problem with them is they reduce, they have a whole series of sort of bad effects that you don't want in a new drug. Ultimately, if you put a mixture of something in, and one of the forms is active and the other one's inactive, you have to put more drug in to make up for it. You have to increase the dose, which can be a problem. The real major problem is that the inactive forms or the other forms that you don't want, they aren't free of toxicity and side effects. They can have real problems for patients. It may be that the active form is totally fine for a patient, and they have a very bad reaction to the inactive form. If you put a mixture in, they'll get that side effect that you don't want. It also causes a lot of problems with drug interactions.
Many patients are on multiple drugs at the same time. Every time you add a new drug to other drugs, you increase the risk of drug-drug interactions and side effects. They can be very serious all the way through to death. Finally, it's very difficult to study these drugs in patients if they're made of a mixture because those mixtures behave differently from one another. As a consequence of all of this, the agencies really pretty much demand that you have only a pure isomer in your formulation. As a consequence of that, there is a whole series of IP implications around that. There have been some examples of where moving from mixtures of drugs to pure drug has actually extended the life of a patent or created a totally new patent.
Plavix, which is an anti-clotting drug, was originally patented back in 1983, a long time ago, as a mixture of the two forms, of the S and the R form of the isomer. It was only patented later, five years later, as a pure isomer. It was discovered that that was the active form. The R form didn't have any activity. As a consequence of that, when the pharmaceutical company that owned it took it to the FDA, they got it approved as a pure isomer. The FDA was happy about that. Ultimately, over the lifetime of the patent, it generated almost $43 billion. This is in money before 2000, when a dollar actually meant something. As a consequence of that, that extra five years added an enormous number of billions of dollars onto the value of that drug. Lexapro is another interesting example.
This is a drug that's used in the treatment of depression. It was approved as a mixture originally. It wasn't known. Later on, it was discovered that only the S form isomer really had any activity, 100 times more potent than the R form. That discovery was patented. That went on to be the S form was approved as a pure S form. Over their patent life, almost $14 billion in revenue. You can see here that doing these types of activities can generate very, very, very large returns for investors. It's sort of the sort of thing that you would like to discover. At that, I will pass it over to Pete to talk a little bit more about the commercial significance and his experience over the years with this exact topic.
Yeah, thanks, Daniel.
I just want to take an opportunity to congratulate Mike and the team down at the University of Wollongong for the incredible work they've done and the amazing amount of value they've added to our business. Looking at this pattern, these discoveries from a commercial point of view, this is basically commercial gold. The ability to patent this and get composition of matter claims on a 45-year-old drug is really quite remarkable, first of all. It really then shuts out any arguments that somebody might possibly develop a competing formulation to RC220. Whilst we've always maintained that we thought that was very unlikely, and I believe that genuinely to be the case, Big Pharma will use any big stick they can get their hands on to try and beat down the price in any negotiation. This makes our position rock solid.
There is no way that anybody will be able to come in and follow our path because of this patent. It is very, very important for RC220. Obviously, it adds to the building clinical data we've got. We've already established, OK, only N of 2 patients, but we've already established that it is safe to administer through a peripheral vein. So far, so good in terms of the safety in the study. The data is building in a very positive way. Now, onto maybe a more significant change, and that is RC110. This drug has worked in AML, where the original bisantrene was approved in France in 1988. We have seen in a couple of studies a very, very good response rate. In recent studies conducted in Israel, RC110 EE bisantrene can get a 40% overall response in AML as a monotherapy.
In combination in much later stage patients, it also showed a 40% response rate. That is very, very similar to the data, in fact, identical to the data LEDLI generated. Just looking overall at the activity, there is a whole range of drugs here with different mechanisms: IDH1 inhibitors, IDH2, a menin inhibitor, and there is a chemotherapy drug, cytarabine. What you can look at here is the response rate, and EE bisantrene RC110 compares very favorably to most of them. Very importantly, it can be used across all of the patients, whereas some of these drugs are really confined to quite small patient populations who have a particular mutation that is being targeted. We think that it has a role to play. Cytarabine, again, a broad chemotherapeutic agent, is similar, but doesn't have anything like the overall response rate.
The point here is that we have phase two data with RC110. It theoretically could enter, once all of the paperwork's been filed, into a registration or phase three trial. We are just really starting to look at the ramifications of that. In terms of partnering, there are some complexities here because if we've got RC110 being delivered by a central line and then RC220 becomes available, there is a risk of cannibalization. We think the opportunity here can be to go to a potential partner with something that's phase three ready. Just to repeat, it is really amazing to have a phase three ready compound with 20 years of patent life. That just does not happen.
This could be quite an interesting, exciting opportunity for someone to take RC110, but also to be partnering on RC220 so that they can get something onto the market very quickly in AML and then follow up with RC220 in solid tumors and maybe transition to 220 in AML as well. I'm just really starting to think about this, particularly now we're getting the safety data coming through on RC220. We've got all the safety data, obviously, from RC110, which is very well behaved. In conclusion, and then we'll be opening up for questions, we've shown these three isomeric forms, EE, EZ, and ZZ. Just again to reiterate, this photoisomerization was not known. Getting back to the strength of the patent, the fact that 45 years has passed and nobody's discovered it and then Race Oncology has discovered it actually adds a lot of strength to what we're doing.
It looks very much to us that only EE bisantrene has any anticancer activity. I think looking at the data, the other isomers do not. We have used EE bisantrene in our formulations with 110 and 220. All the data in the modern era was with the EE bisantrene. We go to a lot of lengths in the RC110 protocol, the current study, to protect the drug from light before it goes into the patient and then to protect the samples. We don't have a situation like Mike showed earlier on where we're losing some of the EE bisantrene because it's being converted to another isomer. We've filed the patents. We've been told by counsel that they feel we've got a very good chance of getting claims up. We're actually going to be going for what's called an expedited review.
We can very rapidly, and it happens in about a period of about eight weeks, actually get an early assessment of the likelihood of patentability. There are always questions in those. They never come back clean. It will give us a pretty good idea of what sort of counterarguments we'll be up against. With that, I will hand back to Jane and we can get into some questions.
Thanks. Excuse me. Thanks, Pete, Daniel, Mike, for taking us through the science and also the commercial potential behind the work that's been done here. I'd like to add my congratulations to the team for getting to this point. It's big news. With that, I'd now like to open up the floor to Q&A. If you'd like to ask a question, the procedure is to pop your question in using the Q&A function in the ribbon at the bottom of the screen rather than using chat or raising your hand. Thanks to those who, the many, who have submitted questions already. Let's start with this one, perhaps for you, Mike. Although the EE isomer is novel, if the processes to create and store it aren't novel, why would those claims be allowed by the patent examiner?
OK, thanks, Jane. That's a really good question. In terms of creating EE bisantrene, in the past, people have synthesized EE bisantrene. That's not new, certainly. What you buy from a chemical vendor in the powdered form will be EE bisantrene dihydrochloride, the salt form. What we've found is that when we tried to scale up, because we're talking about synthesizing multi-kilogram scale bisantrene dihydrochloride, using the known methods, which is performing the last reaction in a solvent called isopropanol, that reaction wouldn't go to completion. There were byproducts formed, really created a lot of problems. We had to find innovative solutions to performing that final step. We switched to doing it in a different solvent, methanol. We found some interesting things, like there was more isomer formed when we made that switch. However, the reaction worked better, less side products.
We figured out a way to push that EZ isomer form back to all EE bisantrene in the process. All of that means that those innovative discoveries were made and allowed us to file one of those three patents, is in fact how to make, how to manufacture pure EE bisantrene dihydrochloride. That was our new innovations there.
Thank you. OK, while you've got the floor, I might ask you this follow-on question. Do the two inactive isomers, and we've had a few questions around this, have zero effectiveness? Or do they have some effectiveness, albeit less than the EE isomer?
Yeah, again, another good question. I showed you on my slides one of the graphs that as you increase the amount of EZ isomer present in solution, you really start to see a drop-off in the activity of the mixture, its ability to kill the cancer cells. While we can't say, we can't put a number on it, we can't say it's zero anticancer activity for the EE isomer, sorry, or the ZZ, because we just can't create pure samples of those compounds. All we can say is that it's absolutely clear that the EE bisantrene is the most active of the three isomers and is possibly the only active one of the three.
Yeah, if I can just jump in there as well, it doesn't have to be night and day. It doesn't have to be zero and 100% between the isomers. All there needs to be is a difference, and clearly, it's a very substantial difference. As I said, I don't think anyone's going to be able to solve that problem of how to test that definitively. I think the important thing to take home is that it only really needs to show a difference to be patentable.
Got it. Thank you. OK.
That answers the utility requirement of a patent. That shows the use at the end of it.
Right. OK, great. OK, so maybe one for you, Daniel. Did the first trial in Israel, i.e., Megla 1, use only the EE isomer?
Yes.
OK, thank you. Short and sweet. There has been some chat on Hot Copper about transforming the inactive isomers into the active one, EE, just prior to administration. Does that make sense? Or will only the active isomer be delivered to where the drug is administered? Mike?
As we heard earlier on, having mixtures of isomers is really frowned upon these days by regulatory authorities. You would have a really hard time getting approval for a drug product that was a mixture. There's not really any point in pursuing that angle and trying to develop a drug product that you would do that, convert it all to the EE isomer prior to administration. In fact, we know that that's not even possible anyway because if you get a mixture of isomers in solution like that, there's no way you can convert it back to 100% EE. I mentioned that we did it in the manufacturing, but that's a different story. That was heating it in isopropanol to get it to all convert back to EE. I'd say that while it may seem like a good idea, it's just not possible or practical to carry out.
Got it. OK, thank you. You would be the expert on these things. We'll go with your opinion. Daniel, how difficult was it for this discovery to be successfully kept confidential for years? Congratulations, it was successfully kept confidential for years.
I guess if you hire professional people who are all with the single purpose of seeing the success of the company, it's not that difficult. One of the things about Race Oncology is that all the employees are shareholders. They all, you know, they want to see the success of the company. They all believe in it. They work incredibly hard to make it happen. It's not that surprising that they understand the importance of keeping this secret until it's the right time to patent, which is the last time. We try and keep it a secret for as long as possible and delay putting in the patent for as long as possible. That maximizes the lifespan of the patent. It's ultimately, yeah, it's both easy and difficult. I guess if you hire the right people, it's easy. If you hire the wrong people, it's difficult.
Yeah, and I would add good corporate governance. So well done. Maybe one for you, Pete. Why did you choose to patent all three together rather than having three separate announcements?
Yeah, I know it sort of does look a bit strange to not try and maximize the number of press releases you can get out. The simple fact of the matter was that each of them contains references to EE bisantrene, and so that would have acted as prior art. Had we not filed them all at the same time, they're sort of interrelated. It might look strange from the outside, but it actually makes perfect sense. It's one of the things that we are always on guard for—what's going into a poster, what's going into a paper, what's going into a presentation—just making sure that we're not talking about something that we're then going to try and patent. Even a disclosure, an investor presentation, can act as prior art. It's deemed published, and certainly if it's presented at a scientific conference.
You have to be very, very careful in this space. I mean, everyone in our industry has to do the same thing. We do monitor very, very closely what data we're letting out and when we're talking about things. That's one of the reasons why we knew about this IP, but we couldn't say anything until patents were actually filed, until everything was in. That's the reason why we filed the three at the same time.
Thank you. Perhaps while you've got the floor, how confident, because these are patent filings that we're talking about here, how confident can you be that these patents will go to ground?
At this stage, you can never say 100% confident because it's always a bumpy road filing a patent. It's almost like the patent officers are being told to reduce the number of patents that are getting granted. In this case, though, looking at the data and people online will have seen a glimpse of that today, it's pretty, pretty strong stuff. As I said, the fact that 45 years has passed and we're the first people to make this discovery means that it's not exactly blindingly obvious because somebody would have stumbled upon it before. I think it's pretty robust. All three of us on here and many others in the company have reviewed the patent filings. Normally, you know, I'm crying my eyes out with boredom after about the first 20 pages. This one actually was quite compelling. I said to the patent agent, I said, it's a ripper.
I think we can be very confident. Just a caution, as soon as you get that first examination, there will be all sorts of comments and questions about, well, what were LEDLI using? Do we know? There will be questions asked. It's always an arm wrestle. Just to caution everybody, it's never a, oh, that looks fine. It'll just be waved through. There will always be some points that are misunderstood or where we have to make an argument. That's par for the course. It's what we do all the time. We'll wait and see that first examination report. That'll give us a very, very good idea. Obviously, we can talk more about that at the time.
Right. OK, Daniel.
I would just add to that that it's not a black and white outcome. There's multiple patents. There's hundreds of claims. We may lose some claim here or there. It's definitely a gray. Hopefully, it'll be close to the black end of gray rather than the white end. You just never know on that. I would expect some claims to get knocked out along the way. I would imagine all the important claims are very likely, in my opinion, to get up. Certainly, the opinion of people far more experienced than me in patent writing share.
OK, thank you. All right, let's move on. Could it be explained, Daniel, why only a poster presentation was offered at ISMO, given the implied significance of the recent news, which has been known for a long time? My understanding is that an oral presentation was a sign of significance.
The presentation at ISMO is around the mechanism of action of anticancer, totally different announcement. Obviously, we couldn't put in a poster of this work before the patent goes in. We can't tell anyone. That would have been a great way of invalidating the patent. The poster presentation, it's a choice made by the ISMO reviewers. They get far more requests for presentation. ISMO is a clinical conference. They'll be biased towards clinical trials rather than preclinical results. It's not actually that surprising. It's just the nature of the way these things go.
OK. There are a few cute questions in here from shareholders, including this one, regarding the blackout, which has been discussed. Is there a real possibility it will be released prior to going to Hong Kong and Berlin? Also, how would you rate the significance of what the blackout is regarding? Thanks for your time, team. Keep up the great work. Daniel?
I've got to love asking a question about a blackout as it means something we can't talk about because it's quite sensitive. By definition, we can't tell you anything about the reason for the blackout until the blackout is over. The blackout will end at some point. In my personal opinion, I wish it had ended long ago because I've sat there watching the share price go up and not be able to buy. I know Pete shares the same frustration.
Very annoyed.
Very annoyed.
Very annoyed.
It's very annoying to want to buy and not be able to buy.
I've said publicly that I want to buy. We can't go into the details of the blackout, but I hope it's over soon. We're working our way through it.
We will obviously have to announce any important, you know, material news to ASX. Are you in discussions, Pete, with a prospective partner presently looking for a better understanding of what the plans and timeline are here? Please map out the current targeted future milestones.
Right. Oh, great. That's quite a bit to unpack there. I might get the future, I'll throw that to Daniel on the future milestones. I mean, I've said this before, and I'll just repeat it. You know, business development is a conversation that stretches out sometimes over many years. As you accumulate data, you go back and you talk to potential partners. As I said, the more data you have and the more robust it is and the better your IP is, the greater the value. I think we could do a deal tomorrow, but I'm not sure it would be at a valuation that would be as we're building enough value for shareholders. I think we can see certainly that what we're doing, and as the data builds, that we're going to be able to do a much more valuable deal.
I think this composition of matter patent will expand the horizon of companies who are prepared to talk to us. You know, 20 years exclusivity. As I said, with maybe the possibility of having 20 years on that phase three ready or even longer with a patent term extension is pretty rare. I think we're going to be getting more attention from more companies. I won't add to that. As I said, we're always talking. We're always talking. We go to conferences, and we're constantly talking. We're sending pieces of information and building that relationship. I've been in oncology for years, so I've got a database with all of the oncology business development people. We know who to talk to. They do tend to move around a bit, so you've got to follow them.
Yeah, look, this story is getting more and more exciting, and that just opens up those commercial doors.
I've got another two questions for you in a row on partnering.
I don't know if that's a good milestone.
Milestones. Go for it. That was for you, Daniel. I think it was.
Milestones. We couldn't. That's a price-sensitive question. We can't answer that outside of an ASX announcement. As much as I would love to be able to give you detailed things on milestones, you'll just have to wait until you see the announcements made.
Though clearly, there's a lot going on with the current clinical.
A lot going on with the current. There's a lot of milestones already out there. There will be future milestones on other activities as they progress. We will update our shareholders as soon as we possibly can by the ASX, as is our legal requirement.
OK, back to you, Pete. Given your current phase one and two trial sites and the new IP position for EE bisantrene, which regions appear most aligned for an initial partnering deal, considering regulatory familiarity, local trial data, and commercial timing?
Yeah, that's a great question. We've talked about exploring regional deals. I think Asia-Pacific, you know, clearly with the Korean site and the Hong Kong sites, follow Korean sites. That can act as a stepping stone into some of those markets. China is the big one, and we're looking very carefully at that. We're having some discussions with parties who can help with performing transactions, those groups in Hong Kong. We've announced that we're going up there for the IGNITE conference, and we're going to be talking to our principal investigators whilst we're there, but also talking to some other groups, investment groups, and brokers up there. I think China is one that we haven't quite worked out what our strategy is there yet, but we know there's value there and evolving value. It's a very, very big user of doxorubicin. We've known that for a long time.
It's an obvious place to go. A lot of conversations going on around that. I think, you know, obviously, the major markets, they actually might take a little bit longer, you know, getting into Europe and the U.S. I think a regional deal somewhere in Asia-Pacific, even China, could actually be first.
OK, follow-on question.
We're not defining any timelines or anything.
Right. Good plan. OK, follow-on though. What would you need in that market to progress from data sharing to a formal partnership?
I think it's building relationships. That takes time. We've identified a number of companies that we want to talk to or are talking to. I've met with a number earlier in the year at ASCO and at AACR. It really is about building that relationship and delivering on milestones. People seeing that the clinical trials are delivering the safety data, they're delivering the efficacy data, they're delivering cardio protection data, and just getting that data out there.
Thank you. OK, this one's for Mike. I would like to ask what protocols are in place for the clinical trials, or perhaps general, depending on how you guys want to put it, to ensure as little light exposure as possible. Are there considerations of the IV line that goes into the patient to reduce light effect? Does body temperature have an impact when EE bisantrene is administered? Let's take that one.
Oh, I assume if you want. Yeah, we've done all the tests to make sure that what's delivered to the patient is EE bisantrene, and all the processes are in place to make sure that that occurs. Body temperature at 37 degrees doesn't cause conversion of EE bisantrene. The body, it's the blue light at the spectrum that causes the conversion. Blue light doesn't really penetrate very far into the body, so you just don't get much conversion of EE bisantrene. As long as what goes in is EE bisantrene, it'll stay as EE bisantrene inside the body.
OK. We've got about five minutes left. We've got about 48 questions in the queue. We're not going to get through them all. I'll just say that. Let's go fast and furious. Mike, one for you. Well done, team. You shared a comparison of anticancer activity for EE and EE/EZ mixtures. Could you comment on the toxicity profile of EE compared to EE/EZ mixtures, please?
Not really, because we don't have to know about the toxicity of EZ because it's not part of our substance or drug product anymore. We haven't investigated the toxicity of the mixture. My suspicion is that the mixture would be no more toxic. Possibly, you know, it's not going to be as active in treating cancer because we know EZ is less active. Based on what we know about mechanism of action, we suspect EZ doesn't perform the same way as bisantrene does in terms of the way it kills cancer cells. We think it's probably a fairly innocuous compound, actually, EZ.
OK. There's a sort of related question. Do the different isomers have different toxicity? We've discussed that. And side effects? I guess there.
It's not all they do. It doesn't matter, Jane, because we only put EE bisantrene in. It doesn't really matter. It could be any other compound that never goes into the patient. It doesn't matter. As long as we deliver EE bisantrene, we don't have to worry about what EE is, properties, EE. Yeah.
From a regulatory point of view, clearly, the ESRS is less, you know, as little extraneous compound into a human. You know, it's logical that's going to be the better outcome for the patient. You know, whether there are any specific side effects of the EE, you know, we won't know.
OK. Quite a few questions, Pete, on how long do we expect the accelerated patent review to take?
It depends on the way you do it. We're going through that process in Australia, and it takes about eight weeks. You pay up front for that, but actually, then you get that's like a down payment for other parts of the process. I'm not sure we've actually initiated that process yet, but the intention is that we'll do that in the not-too-distant future.
OK. I'm going to give this one to Pete. Where do you see the most enduring possibilities for this treatment? What current stroke future treatment would it be displacing?
It's going to be an add-on, clearly. You know, where we're focusing at the moment is with doxorubicin, and we're looking at a number of potential indications where that could be advantageous. There are areas, situations like breast cancer, for example, where doxorubicin is used in the neoadjuvant and adjuvant settings, depending on what type of breast cancer the patient has. Clearly, those patients now have a very long life expectancy. Some of them, I mean, some do succumb quite quickly to the disease. Clearly, that's a group where you've got younger patients living for a long time, where cardiovascular problems are going to be there for a long period of time, affecting the quality of life. That will be a setting that we're thinking about and others. I think that's actually an evolving story, and we'll be talking a lot more about that in the future.
Thank you. OK, we've got two minutes to go. I'm going to take this offer, this last question to Daniel. Perhaps I might turn back to you, Pete, for some closing comments. Daniel, I missed the window for my bonus options. Any chance of buying those still?
Yes, you can go to your broker and go online and buy Race Oncology shares. You will then own your share. You can spend your money that way. You won't get as many as if you took up your bonus option, unfortunately, but you'll still own a share of Race Oncology. The answer is no.
Thank you.
The bonus option expired a year ago. It's more than a year ago.
If I was not being allowed to buy, I would have had bonus options as well. You know, count yourselves lucky those who did that.
Yeah, luckily, we had 82% take-up. I was really pleased. Most people took it up. Obviously, that meant that 18% of shareholders didn't take up their options. I'm sure most of those 18% are kicking themselves now, I hope anyway.
OK, let's not rub that in. All right. There are so many questions left in the queue. I'm sorry that we haven't got through them all. We will endeavor to get back to people on the primary things that keep coming through. Keep an eye out for that. With that, Pete, I might hand back to you for any closing remarks.
Yeah, so again, credit to the team at Race Oncology for this really amazing discovery. Again, bear in mind, a lot of people have been working on bisantrene for decades. They didn't diligently pursue what Mike and the team had done. I've said before that Race Oncology is an amazing group of people. Genuinely, everybody is engaged. Everyone wants to drive forward, get the outcome, deliver things to patients and shareholders. It's been a lot of fun over the past couple of years with this story evolving. I want to thank our shareholders as well. We've got a lot on the line at the moment. We can't do it without your support, so we greatly appreciate that. Hopefully, we'll be able to deliver. Thank everyone online for turning up today and for your interest. Jane, thank you very much indeed. Well compared. Thank you. Thanks, everybody.
As I said, we'll try and get to some of the questions that we weren't able to answer through Investor Hub or other fora.
Perfect. OK, with that, I'll add my thanks to all of you for presenting tonight, the many shareholders that are online and investors broadly. I'll invite you all now to disconnect. Thank you. Have a good night.
Thank you.
Thank you.