Okay. Thank you everyone for attending this session. My name is Fahar Merchant. I'm President and CEO of Medicenna. First, I'd like to thank Bloom Burton for inviting us today to present. I look forward to sharing with you our programs in the clinic, including an exciting new program that we just presented, or just finished presenting in San Diego two minutes ago.
Medicenna is a clinical-stage company. We are publicly listed on the TSX. We have a couple of programs in the clinic with a third program soon to enter the clinical trial. I'll focus really on the top two, which is these are the ones that are generating more of the data and news flow in the coming quarters. MDNA11, this is a program which is in phase I/II clinical trials and intended for treating patients with a number of different solid tumors.
What we have seen really remarkably with this particular drug is that it has shown single agent activity in tumors that have never been tested before with an IL-2 program. We're seeing response rates between 30%-40%, either on its own or in combination with the world's blockbuster drug, KEYTRUDA. We will be updating data on this for the rest of this year.
We'll demonstrate proof of concept with this particular drug, as well as have a meeting with the FDA at the end of the year to decide which phase II program we can pursue in a registrational trial, meaning that a phase II would be a pivotal clinical trial for this particular drug for a specific indication. The second program that's soon to enter the clinic before the end of this year is MDNA113. There is a lot of commonality between MDNA11 and 113.
I'll give you a bit of briefing on that, and this is really a first-in-class bispecific anti-PD-1, and I'll talk about that as well. It's really one of the most exciting spaces in oncology today, and I'll share with you why our drug 113 is by far the best-in-class. The data on this particular program were just presented this afternoon in San Diego, and I will share with you the monkey data with this particular drug, with a plan, as I say, to file an IND before the end of the year.
Finally, I won't talk about this, but really exciting program, which is bizaxofusp (MDNA55), finished a phase II-B clinical trial with very impressive results in patients with recurrent unresectable glioblastoma, where we were able to demonstrate doubling of median survival from about seven months to 14 months in this very difficult patient population.
Again, we are seeking to partner this program, so there's in effect this is a program that we hope to start by the end of this year in a phase III registration trial with a partner. Okay. Separately on MDNA11, fortunately, we have another program that's going on in patients who are newly diagnosed, who are patients who can get surgical resection of their tumor with patients with melanoma or skin cancer.
Here, this program is fully funded by the Melanoma Foundation in Italy, where they're conducting a study in 12 different hospitals across Italy to treat patients with our drug in combination with Bristol Myers Squibb's drug nivolumab or OPDIVO. The intent there is to delay surgery by eight weeks, treat the patient with our drug, and then remove the tumor, hoping that the tumor will not come back.
This is important because I'll share with you some data on MDNA11 that shows us as to why we think this may happen. This is our pipeline. I'd say we are by far a leading company in the space of cytokine engineering. I'm basically going to mention that today I will probably be focusing more on MDNA113 because we've got brand new, fresh, hot off the press data, and that will be the focus today.
Before I go into MDNA113, I think it's really important that you all understand MDNA11. This is an IL-2 superagonist we in-licensed from Stanford University and have developed this into a unique mechanistic drug that's clearly unmatched in this particular category of drugs. There has been a lot of effort in this particular space.
As you can see, over the past 25, 30 years, there's been a lot of effort in developing a drug, which is an IL-2, which is a safe, efficacious IL-2. Unfortunately, as you can see, the first drug that was approved in 1998, called Proleukin, consisted of an IL-2, which is not different from the IL-2 that we all produce naturally in our cells. The purpose of IL-2 is really to stimulate your cancer-fighting immune cells at high doses. At low doses, it does exactly the opposite.
It actually prevents your cancer-fighting immune cells to be active, but instead protects your body against yourself. If you have, let's say, autoimmune disease, you use really low doses, you stimulate a different kind of immune cell, but high doses, you stimulate your cancer-fighting immune cells. Unfortunately, this particular drug is not used frequently, although it did show 5%, 10% of the patients getting cures.
The problem was you need to treat patients 3x a day for five days in a row, but in an intensive care unit. Why? Because the drug could kill you. All right? That means you are really restricted into what kind of patients you can treat. Not surprisingly, knowing that IL-2 has the potential to stimulate cancer-fighting immune cells, the question arose from Big Pharma.
As you can see, Roche, Bristol Myers, Sanofi, et cetera, have invested billions of dollars in this particular program over the past five to 10 years. Unfortunately, without any success. Lots of failures. Lots of programs abandoned. Lots of investors' money gone down. I think the key thing here is what we did was very unique, completely opposite compared to what everybody else was trying to do, and this is where Stanford University's approach was unique.
We approached it in a different way, where we engineered the molecule so that it is designed first and foremost to stimulate cancer-fighting immune cells. It was designed also to be ultra safe. Third, it was designed so that it would accumulate in the tumor and the tumor-draining lymph nodes. I won't go into too much detail here. I don't know if I can use a pointer here. Can I? No.
Okay. What you see here is the engineered IL-2, which is what we've engineered, completely different from everybody else's. We linked it to albumin so that now it can accumulate in the tumor, and that's where it can stimulate your cancer-fighting immune cells. When we did that, what did we see? Suddenly, we're seeing responses. Patients have failed these blockbusters. We call them immune checkpoint inhibitors or anti-PD-1 drugs.
They have become big blockbusters. KEYTRUDA, for instance, which is a Merck's drug, sells about $30 billion worth of drug every year. Bristol Myers sells OPDIVO, about $15 billion a year. Okay? These patients, unfortunately, fail. Those two big blockbusters are used mostly in patients with early stage cancer when they're newly diagnosed. Only 30% of the patients have a response, meaning the tumor shrinks by more than 30%.
$45 billion a year in sales, only one out of three patients benefit. Whereas here, those same patients who failed the checkpoint inhibitor, getting our drug, MDNA11, on its own, we're seeing response rates of 30% in second- and third-line treatment. Just imagine what could happen if we took MDNA11 into first-line.
Okay. This is really exciting. We're seeing the same thing when we combine with pembro, which is KEYTRUDA, and we're seeing response rates of 43% there. Keep that thought in mind, and we now take that learning that we have by far the best-in-class IL-2 out there in clinical development. We'll complete the phase I/II trial before the end of the year and approach the FDA to see how we can pursue with a phase II registration trial with this IL-2.
Now, in order to give you some context here, let's talk about the next molecule. It's not in the clinic, but it will be in the clinic at the end of the year. What have we done here with this particular approach? We have, by the way, so the green circle that you see there in this image is the same IL-2 that it is in MDNA11, which has already shown activity in 30%-40% of the patients who failed first and second-line blockbuster therapy.
We also know one thing. The KEYTRUDA and OPDIVO drugs are going to expire, patent protection is gone, in two years. That's $45 billion loss in sales. What is going to replace KEYTRUDA and OPDIVO? Of course, the generics, the biosimilars.
If you had something way better than KEYTRUDA and OPDIVO, those obviously then become your first-line treatment. There is now this incredible excitement about this new space of anti-PD-1 bispecifics. What the intent is to take the checkpoint inhibitor, anti-PD-1, and fuse it with another molecule, another therapy.
A number of transactions have taken place, as you see on the left-hand side of this slide, where over the past 18-24 months, deals around these bispecifics have amounted to about $38 billion. $38 billion. Why? Because there's this big $45 billion opportunity that's soon to go off patent in two years.
One of them was a deal where the anti-PD-1 was fused to an IL-2, developed by a company called Innovent in China, the drug called IBI363. That October last year, Takeda licensed that for a total deal size of $11.2 billion, with $1.2 billion up front. These guys are obviously ahead of us. Takeda is ahead of Medicenna.
They are already in the clinic. What chance do we have as a company? The thing is this, that you need this approach. There's plenty of room for more than one player. Okay? There's plenty of room for more than one player. It's important to do this. Why are we doing this anti-PD-1 IL-2 combination? Why is it so important?
Now, when you're fighting a war against cancer and your T cells are exhausted, you want to prevent your T cells from getting exhausted, and this is where your anti-PD-1 comes in. This is where OPDIVO comes in. This is where KEYTRUDA comes in. That sort of prevents the immune cells or the T cells from getting exhausted.
Just not getting exhausted is not enough to fight a really deadly battle with a tumor that has so much resources to find ways out about it. You need to build an army. You need to have more T cells. What gets more T cells? You need more T cells, and this is where IL-2 gets more T cells. When you have two things happening at the same time on the same T cell, so you can see this blue structure, light blue circle, that's your T cell.
When you stimulate the T cell with IL-2, so it's about to proliferate, and at the same time, you bind to the PD-1 so it doesn't get exhausted, then you've got the best of both worlds in one molecule, in one drug. That's the reason why there's so much excitement around this approach.
As I said to you earlier, this IL-2 is deadly. Okay? This IL-2 is deadly. It's very toxic. To get around it, we decided to do a different thing. We said, "You know what? The anti-PD-1 blockbuster is going off patent in two years. Why are we creating our own new anti-PD-1? We don't need to. Just use this drug off the shelf. It's available. We'll get that." Second, IL-2. We've already shown with MDNA 11 that we have the best IL-2 out there.
It's safe, it's potent, it's effective, so if we link the two together, that makes it a really powerful or a supercharged KEYTRUDA or a supercharged OPDIVO here with this particular drug. The thing is this, you have a different dose. When you treat patients with KEYTRUDA, you need to treat those patients with about 200 mg every three weeks. 200 mg.
With MDNA 11, we get the effect at 90 μg. That's a huge difference, right? Now, suddenly, if I'm going to go and say, I'm going to take a drug that you need to dose 200 mg, attach 1 molecule of IL-2, you are effectively delivering IL-2 at also 200 mg. That's a lot compared to 100 μg . We need to take action. Others have to do something else.
If you're going to use IL-2, you've got to do something that makes it silent or dampen its activity. All our competitors, what they've done is they've engineered the IL-2 so that now it becomes weak. It becomes weak. When it becomes weak, it's not effective. We have shown that you need a potent IL-2 to do the job.
What we've done is we've created an approach. We are masking our IL-2. We are putting a shield around our IL-2, and that shield hides the drug as the drug is traveling through your body, through the blood, eventually getting to the tumor. At the tumor, it switches on. But how do you know if the drug is going to switch on or not? Okay. To ensure that happens, we need to make sure the drug gets stuck in the tumor.
For that, we use this approach where we call targeting. By targeting and accumulating the drug in the tumor, we ensure that we can switch the drug on. This looks complicated. I can assure you it's easy to manufacture. Okay, the green thing here is the IL-2 from MDNA11. We haven't changed it. It's the same thing.
The white and purple structure is the anti-PD-1. This is the blockbuster OPDIVO or KEYTRUDA. We actually have studies going on with both. Okay. Both of them are looking head-to-head just as good. We'll eventually obviously pick one of them and take that into a clinic. That's your anti-PD-1, that's your IL-2, and then that sort of orange, yellowish structure on the left is a masking domain. It's sort of hiding the drug, so it's not active.
Then the structure on the right is a ligand that binds to a receptor. It's known as IL-13Rα2 . That receptor is found in so many tumors, and it's associated with more aggressive tumors. If a patient has a tumor that has a biomarker for IL-13Rα2 , that patient has a more aggressive tumor.
Okay, what we're doing is we are targeting, so the drug now accumulates at the tumor so that we can then switch on the drug. How do we do it? By the way, why are we looking at IL-13? Why are we looking at this particular target? As you can see, whether it's liver cancer, brain cancer, ovarian, pancreatic, lung, et cetera, these tumors, by and large, the majority of patients have this particular target. The biomarker is IL-13Rα2 .
What is interesting is that you can see those two slides on the right-hand side, the colon cancer, and the lung cancer. Patients that don't have the IL-13Rα2 , they have a much better survival outcome. Those that do have the receptor, they die very quickly because the tumor is so much more aggressive.
This is a huge unmet need. Approximately 2 million patients every year are diagnosed with this type of receptor tumor. That's a huge number of patients, okay? Now, just to show you how our drug works. This is mice, and what you see is those two pink structures. Avoid the orange ones. The two pink structures on the left is a tumor that does not have the IL-13 receptor. On the right where you see the plus sign, this is where the tumor is expressing the IL-13 receptor.
We treat the patients. You can see after 72 hours, the drug is accumulating. It's still there. It's in the tumor for three days at least. Okay? That means this is something that we are able to localize the drug very effectively. How does the drug work? Basically, the pink structure binds to the receptor.
Once it's on the receptor, you see these Pac-Man-like structures. They actually cut the linker, release the drug, and that drug then binds to the T cell, where the anti-PD-1 prevents the immune cell or the T cell from getting exhausted. Our IL-2 stimulates the immune cells to proliferate and do their job. This is how unique this is. What's happening is we are able to keep the drug safe in systemic circulation and get switched on at the tumor site.
The interesting thing is, I won't go into this much detail, but one other thing is, people will say, "Fahar, well, you need the protease to be there." Well, what if there's no protease? What if there's no Pac-Man around to cleave the drug? What we have found that even in the absence of this Pac-Man, what happens is when the drug binds to the PD-1 receptor on a T cell, because now the whole molecule has so close proximity to the immune cell, our IL-2 will automatically bind as well, because we've engineered the IL-2 to bind very tightly to the beta receptor, which is found on T cells.
So we have a backup mechanism here. So the key thing here is now let's go back to our competitor, Innovent, Takeda. They have a drug that is anti-PD-1. It's their own anti-PD-1. It's not OPDIVO, it's not KEYTRUDA.
It's their own anti-PD-1. They have their own IL-2. Okay? It's not our IL-2. They can't use ours because it's patent protected. They've got their own IL-2. That IL-2 has never shown single agent activity, ever. They've never even tested their IL-2 in humans. They don't even know whether it works or not. Okay? What we do see is patients potentially dying of this drug because it is so toxic.
We call it Grade 5 events. Okay? This is an issue with their drug, whereas we wanted to make sure our drug is safe. Okay? That's the way we designed it. The question is our drug really safe? I mean, how do we know whether it's safe or not? What are the key features of our approach? We are basically very engineered IL-2 that's worked.
It's targeting, so it accumulates at the tumor site, and we've got two switches. Switch on the drug at the tumor site. Nobody else has that feature in any of their bispecifics. There's a whole bunch of other key features of this drug that make this drug a lot more safer, a lot more efficacious. What we did was, to be fair, we said, "You know what? Let's make our drug, and we also make our competitor's drug.
" Right at the bottom, you see on this table is the competition drug, which is basically the anti-PD-1 with their IL-2. Because it's a patent, it's published, we can make that same drug. We tested the drug in non-human primates, meaning monkeys. What you see here is we are able to dose at 10, 30, 50 milligrams per kilogram.
With their drug, they're down to 1.4 mg. That's 30-40 times lower dose, and these monkeys were so sick after the first dose, we could not even treat these monkeys again to a repeat dose. That was a big issue here that's consistent with what they have published in human clinical studies. What we also show in this monkey is the dotted black line and the gray boxes is the weight loss. Within two weeks, the monkeys lose normal, almost 20% of the weight because it's so toxic and they can't eat. You see this thing also in mice.
If you see on the extreme right, you can see that most of the mice died before the second dose, whereas with our drug, where you can see those green, blue, and pink colors, this is our drug, not at 7 mg or 21 mg, but 100 mg per kilogram, right? We are dosing multifold times higher and seeing these remarkable safety features of our drug.
Then when we try and use human immune cells and see how our drug does, we can see our drug does much better. If you look at that pink plot, we're seeing an exceptionally high stimulation of CD8+ T cells, whereas the red boxes is our competitor's drug. It doesn't do a good job. We're also stimulating gamma delta T cells. These are the ones that will fight cancer effectively.
Overall, we're seeing whether it's the liver, if it's a kidney, you can see the urea levels really spike incredibly high levels of urea in these patients that have received the competitor's drug. Also from the immune system, you can see all these other immune cells being highly activated with this drug.
Overall, what we have demonstrated here in a head-to-head comparison, whether it's in human immune cells, in mouse, in monkeys, all of those, our drug is substantially safer by manifold than the competitors, where Takeda paid $11.2 billion. Then, of course, the drug is active. You can see that we are able to demonstrate pretty much complete responses with one or two doses of our drug. Then when we rechallenge the mice that were cured with this drug, we find that when you rechallenge, these mice never have a tumor to show. Okay.
This is consistent with one of the patients we treated with our pancreatic cancer patient in the phase I trial with MDNA11. That pancreatic cancer patient stopped receiving our drug in December 2023. As of today, that patient's tumor is still gone. It's not showing up. We have, we think, curative potential with our IL-2. We think our 113 will do even better with this approach that we have taken in terms of designing a better, safer, more efficacious drug. We look forward to taking this program in the clinic. I'll stop here. Thank you. Okay. I think I am off time.
Very nice work. Beautiful data. My question is, once you combine these three protein, like a fusion protein, you may generate a newer epitope, particularly after anti-PD-1, you may generate significant immune response.
Yeah.
Maybe target our drug, your drug. Could you please comment how long time-
Yeah
You could see, for example, undetectable antibody, anti-drug antibody?
Right. We haven't shown those data today, but if you look at the PK data we saw from first and second doses, there's no change. We believe there's no anti-drug antibodies being generated. Of course, we'll see that in humans as well. So far, we are looking like it's pretty clean. Okay? All right. Thank you very much.
All right. Thank you all very much. Please welcome me in giving Fahar a warm round of applause.
Good talk. Antonio.