Next, we have Medicenna Therapeutics. It trades on the OTCQX under the symbol MDNAF, and on the TSX under the symbol MDNA. It's a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4, and IL-13 superkines, and first-in-class empowered superkines. Happy to welcome President and CEO Fahar Merchant. Welcome to the Congress today, Fahar.
Thank you very much for having me.
All right, the floor is yours.
Okay, thank you very much. Glad to be here. Thank you for all of you who have joined in this morning or afternoon, wherever you are. Just to let you know that Medicenna is really focused on a series of molecules we call cytokines. These are engineered cytokines. We use the technology from Nobel Prize-winning work done in 2018. These are evolutionary cytokines. The purpose here is to really generate, we believe, revolutionary medicines for treating not only cancer, but other diseases as well. Just as a good housekeeping, just to let you know that I'll be making some forward-looking statements today. I encourage you to look at our filings and on SEDAR. Starting off with the programs that I'll talk about today is essentially based, as I said, on what we believe are first and best-in-class superkines.
What are superkines? Really, superkines are these engineered cytokines. Cytokines are almost like hormones, really. They really control, they manage, they modulate our immune system. In the case, let's say, if you had infection, our immune system would be really supercharged. In the case of a situation where we have, say, autoimmune disease, we will have an immune system that's going to attack our own organs, et cetera. Having a properly balanced immune system is crucial. Unfortunately, when we have autoimmune diseases or cancer, for that matter, that's where our immune system is failing us. That is where we are developing these superkines to help us treat these patients with either cancer or autoimmune diseases, et cetera. Today, I'll talk really about cancer. I'll talk about, first and foremost, our lead program. It's called MDNA-11. It's an IL-2 superagonist.
This is currently in phase I/II clinical trials. The data look really promising in that in patients who have failed different checkpoint inhibitors, we are seeing response rates of anywhere from 30%-50% with our MDNA-11 on its own. I'll move on briefly to talk about another really exciting space that's becoming, you might have seen a number of news flow just this week. We had Pfizer announce a $6 billion transaction with a Chinese company. This is where the focus is on generating what we call these bispecific checkpoint inhibitors. These are bispecific anti-PD-1. I'll talk today about our own bispecific anti-PD-1 called MDNA-113. We believe that, again, is a first-in-class molecule that we'll talk about later on.
The third program that I will not mention much today, it's a program that has generated really promising data in phase I and II clinical trials. It is a first-in-class IL-4 superkine. This program essentially has an engineered interleukin 4, which carries a very potent toxin. We have seen really impressive results in patients with very aggressive forms of brain cancer called glioblastoma. This particular program is now phase III ready, with the potential for this program, or this particular asset, being used for other brain cancers as well, with a very large revenue potential of about $4 billion or so. This program, we are looking to partner this. Overall, when we are from a cash position, we have a healthy cash balance, taking us past middle of next year with several catalysts coming up, most of them before the end of this year.
We believe there's a number of data readouts we'll have. We'll be keen to share those with you in the next six months or so. Moving on to our, let's see, where are we? Program here, just briefly talk to you about the superkine platform. Just very briefly here, we've taken cytokines interleukin 2, 4, and 13, and really engineered this using this directed evolution approach. This allows us to generate superagonists or even superantagonists. In cancer, we need a superagonist. In the case of autoimmune disease, we need a superantagonist. Each of these programs is capable of generating a pipeline and a product. Multiple opportunities with each of these interleukins or superkines we're generating. Moving on to the pipeline that we have, we believe we have a really well-balanced pipeline addressing the three different superkines.
More importantly, we cover early, mid, and late-stage assets. Starting right at the top, I mentioned to you MDNA-11. I'll talk more about it. We'll have multiple readouts in the second half of this year. It's currently in the phase II portion of the clinical trial. We also have, with our MDNA-11, a separate arm where we are enrolling patients. We are combining MDNA-11 with Keytruda. It's a checkpoint inhibitor. It's the world's biggest selling drug. This is a combination study where we are collaborating with Merck. The third program, which I mentioned to you earlier on, is essentially around bifunctional or bispecific checkpoint inhibitors. This is an anti-PD-1 IL-2 program. This particular program, we believe, will be ready for IND enabling studies towards the end of this year, so we can start clinical studies next year. The other programs are earlier stage.
One of them is for autoimmune disease, the other one for inflammatory diseases. As I mentioned earlier on, MDNA-55, which is our Bizaxofusp molecule, it's an IL-4 fused to a toxin with really promising data in glioblastoma. This particular program, we are looking to partner this asset. We'll focus first and foremost on MDNA-11. As I said, it's a clinical-stage asset, the monotherapy and combination arm, the combination portion being in collaboration with Merck. Before I go and talk to you about MDNA-11, let me sort of give you a bit of background on this particular cytokine or interleukin 2. Interleukin 2 was the very first immunotherapy ever approved for treating cancer. This drug was approved in the 1990s for treating patients with either melanoma or kidney cancer and provided response rates in the 15%-16% range.
Amongst those patients, there was about 5% or 6% of patients that had long-term cures, in the sense that tumors would not come back for 5, 10, or even 15 years. Really exciting particular molecule. The response rate was not that great. Even more challenging was the fact that this particular molecule was incredibly toxic. This toxicity meant that patients had to be administered this drug in an intensive care unit because the drug was so potent, it had so many poor side effects, it could kill a patient. The second big challenge was this drug did not stay in your bloodstream for long enough, and it needed to be administered every eight hours for five days. Really not something that got traction and was used very infrequently.
What the scientists at Stanford University did was sort of created an engineered version of the IL-2, generating what we call this IL-2 superagonist. The intent here is really to get much better efficacy, but at the same time, have a much better safety profile so that patients can accept and receive this drug in a setting where patients are not in an intensive care unit. What you can see on the left-hand side, the cartoon basically shows that this molecule has been altered in such a way that it will bind very selectively to immune cells that have this receptor known as the beta-gamma receptor. That beta-gamma receptor is really responsible for attacking tumor cells. Those are the ones that we want to stimulate.
However, the ones that are on the left-hand side that also contain the alpha receptor, those are the ones that will stimulate the immune system. But in addition, they will stimulate immune cells known as Tregs, which will actually protect the tumor. The other thing is that the binding to the alpha domain also causes undesirable safety profile of the drug. What we've seen so far with MDNA-11, as I'll explain later on, we're seeing 30%-50% of patients responding to MDNA-11 on its own. We've seen 100% reduction of tumors in three patients. We are also seeing a very desirable safety profile. Really importantly, we're not treating the patients three times a day, but in fact, once every two weeks. We've got a molecule that's got unique pharmacology, balancing safety and efficacy. How have we sort of achieved that?
Essentially, what you see on this cartoon is that on the left-hand side is the engineered IL-2. We have inserted a couple of mutations where the molecule is no longer able to bind to the alpha receptor. That will mean that this particular IL-2 will not stimulate the cancer-protecting T regulatory cells and also will avoid the safety issues. The second thing we did was insert five mutations to substantially enhance binding to the beta receptor. By doing that, we are able to stimulate the cancer-fighting immune cells. Also, what we found is that we are able to stimulate what we call memory immune cells. These memory immune cells stay in our bloodstream for a very long time. If the tumor comes back, the immune cells are ready to attack the tumor again.
Finally, what we did was we linked our IL-2 to albumin. Albumin is a large molecule, which means that it will not clear your kidneys very quickly. Therefore, the drug stays in your bloodstream much, much longer. In this way, we are able to treat patients once every two weeks. The other big advantage about albumin is that it tends to accumulate in the tumor. Even more importantly, it accumulates in what we call the tumor-draining lymph nodes. This is where the immune system gets trained to fight cancer. Overall, we have sort of incorporated in MDNA-11 a number of key features that make the drug more efficacious, safer, and generate immune system or immune responses that are long-term. The trial that we are conducting right now is what we call the AbilityOne clinical trial.
This is a phase I/II clinical trial. We have finished the phase I portion of the study. What we did was initially conducted the phase I with MDNA-11 alone, and then subsequently conducted a phase I study with MDNA-11 in combination with Merck's drug Keytruda. In both cases, we identified the 90 microgram per kilogram dose as being the ideal dose that we are now in the phase II portion, where we're using the same dose of MDNA-11, either on its own or in combination with Keytruda to treat a number of different tumor types. On the right-hand side, you can see a list of different tumors. The first one at the top is melanoma. The second one is MSI high DMMR tumors. The third one, TMB high.
The fourth one, in the case of monotherapy, we are treating patients with tumors that are evolved as a result of viral infection. In the combination setting, looking at a combination and sort of looking at specifically gynecological tumors. The reason we picked these tumors, especially the first three tumor types, is that each one of them would be patients who have failed checkpoint inhibitors. Currently approved checkpoints are not, these patients are not responding to those therapies. Second of all, there is a pathway for accelerated approval, meaning that through a phase II clinical trial, a single arm could generate a sort of approval with either on its own or combination for these three different tumor types. That is where we have, we know what the benchmarks are for melanoma.
For instance, if we get response rates in the 30% range, that would be sufficient to get to that threshold with the MSI high and TMB high. These are biomarker-driven. Essentially, it's not a particular organ that has this particular tumor type. There are sort of dozens of different solid tumors that have this biomarker known as either MSI high or TMB high. Therefore, you can treat so many different tumor types. These patients would have failed checkpoint inhibitors. Here, the threshold would be to secure response rates in the 20% range. Looking at safety, we're seeing a really desirable safety profile. We did not see, even as high as 120 micrograms per kilogram, any dose-limiting toxicities at any of the cohorts, either on its own, monotherapy, or in combination with a checkpoint inhibitor.
By and large, as you can see, the adverse events were generally of grade one and two. More than 90% of the adverse events were grade one and two. There were a handful of grade three, four events. We can see that that was the case even in the combination setting as well. We are not seeing any new adverse events in the combination setting. Whatever we are seeing in the monotherapy is what we would normally expect with IL-2 molecules. The important thing here is that the safety profile, most of the adverse events are low to moderate. More importantly, they are of short duration. These adverse events go away in 24-48 hours.
The other thing what we found is that as we had designed the molecule, what we end up seeing is really exactly what we were expecting, is that we were preferentially stimulating the cancer-fighting immune cells, namely the CD8 T cells. You can see the expansion of CD8 T cells quite dramatic, whereas the Treg, which is sort of the gray, virtually does not even show in this particular slide, showing that we are really boosting the cancer-fighting immune cells more effectively than the Tregs. It is not only the cancer-fighting immune cells that we are stimulating. It is not only the quantity of these immune cells that we are boosting, but it is the quality of these immune cells.
Here we are seeing that when we look at the very specific subsets of these immune cells known as CD8 T cells, which are the ones that are the most prolific, the most potent cancer-fighting immune cells, we see a dramatic increase when we compare to baseline to day eight, with each of these immune cells showing that these are much better cancer-fighting immune cells. They have these certain markers known as DNAM or TCF. This means that these immune cells stay in our system for a very prolonged time. We also see the same thing with memory to CD8 T cells, meaning that these immune cells will allow patients to have a treatment and receive therapy, but the durability will be prolonged so the tumor does not come back very quickly, which is what we see in our clinical trial.
Based on that, if we look at the data we have generated so far with MDNA-11, this is MDNA-11 on its own. This is in patients who have failed at least one, if not two, in some cases, three different checkpoint inhibitor therapies. These patients, you can see, have prolonged and durable clinical benefit. This is really important, particularly if you look at the very top, the very first patient there, this is a patient with pancreatic cancer. This patient initially had surgery, subsequently received a cocktail of four different chemotherapy drugs. The tumor continued to advance and eventually metastasize and spread to the liver. The patient then received another combination of two different chemotherapies. The patient was not able to tolerate. Finally, received Keytruda. That Keytruda itself continued to show that the patient was progressing. The patient entered our clinical trial, received MDNA-11.
By the first scan, we saw the tumor was stabilized. By the second, third, fourth scans, we can see the tumor shrinking. Eventually, the tumor shrank to about 70% or so. The patient went away on vacation, came back after eight weeks of holidays. Unfortunately, there was a new tumor that showed up. The patient was briefly treated with radiation for just one cycle and started MDNA-11 again. What you see is that that patient's tumor completely disappeared, not only the ones that were in the liver, but even the new one. That patient has been off therapy now for about a year and a half. There is no sign of the tumor coming back, which is consistent with what I mentioned, this potential, the curative capability of a drug such as MDNA-11. We're seeing the same thing with a number of other patients.
Hopefully, as you can see from this particular slide, we are seeing very impressive, in fact, remarkable responses in patients ranging anywhere from 30%-50%. In some cases, a couple of cases, as you can see, the tumors have completely disappeared. Really encouraging data we've seen so far. In patients with MSI high tumors, for instance, we are seeing a response rate of 50%, which is really impressive amongst patients with secondary resistance to immune checkpoint inhibitors. We're seeing response rates of about 33%. Amongst all those patients who are eligible for the phase two portion of the trial, we're seeing a response rate of 40%. Each case, we're seeing really promising results. When we look at the combination setting, again, we're seeing response rates of 30%-50% in different tumor types. These are patients with gynecological tumors.
We're seeing, for instance, patients with endometrial cancer, where these patients would not normally respond to a checkpoint inhibitor. We're seeing a 50% response rate. In a patient with anal squamous cell carcinoma, where checkpoint inhibitors really do not show much responses, it's usually a 5%-6% response rate. We've already seen that one patient have a complete response after the first scan. We're also seeing patients with other tumor types, including colorectal cancer, melanoma, et cetera. We're seeing response rates of about 36%. Each one of those are really exciting data sets. We're seeing responses in tumors that normally do not respond to checkpoint inhibitors. We're seeing these responses to be durable. Overall, the key highlights here are that MDNA-11, either on its own or in combination, is generating response rates in the 30%-50% range.
We're seeing really promising safety and efficacy in the combination setting. We are able to treat patients once every two weeks, which is so much better than treating patients three times a day. Overall, we continue to advance this program. We'll have more data coming up in the next two quarters. These will be key value inflection milestones for us in order to prepare us for a phase two registration trial. Moving on to this other new program that I briefly mentioned to you, this is the bispecific checkpoint inhibitor, MDNA-113. What is this excitement around? As you can see from this particular slide, PD-1 inhibitors, such as Keytruda or Opdivo, are today the best-selling drugs. Keytruda, particularly, is the number one selling drug. In 2024, annual sales were $30 billion. These drugs are expecting their patents to expire in 2028.
That includes Opdivo, which sells for about $12 billion. The thing is this: as this patent cliff is just around the corner, there's an attempt to create these bispecifics, where these checkpoint inhibitors are fused to other candidate molecules, such as VEGF, and we are working with an IL-2. You've seen multiple transactions. Each of these are either in early stage or mid-stage clinical trials. You see transactions of Merck, Summit, BioNTech, et cetera. Each one of those, you can see these are multi-billion dollar transactions. Just this week, we had Pfizer enter into a deal with 3SBio from China in a $6 billion transaction with $1.25 billion upfront for their bispecific. What we're doing with our drug is quite different. In fact, we are taking an anti-PD-1, which is already approved in the marketplace. We are not experimenting with new anti-PD-1s.
The second thing is we've fused it. That green dot that you can see, or the green circle that you see, is our IL-2, which has already shown single-agent activity on its own. The pink squares that you see is our IL-13. This is really unique in the sense that it sort of allows the drug to be targeted to the tumor because the IL-13 will bind to a certain receptor on cancer cells. It only binds there and not healthy cells. Once it's located there, the IL-13 is cleaved off. The drug is activated. You switch on the drug right at the tumor site. You can see what's happening on the left-hand side. The molecule, the IL-2, is masked. As it gets in the tumor site, it is unmasked, gets activated.
That is where we find the key major advantages of our drug with MDNA-113 and other bispecifics that we are working on, is that we have a number of key advantages compared to other bispecific checkpoint inhibitors. The reason we are pursuing with the IL-13 version is that every year, about 2 million patients are diagnosed with tumors that express this particular antigen known as IL-13 receptor alpha-2. You can see that this is an opportunity for us to really treat patients with this, what we call cold tumors, where checkpoints on their own do not work, and for us to address this huge unmet market. Just for those who are not familiar with the checkpoint space, we know one thing is that with checkpoint inhibitors, about 30% of the patients will benefit. The remaining 70% do not.
The majority of these are these ones that you see here with the IL-13 receptor alpha-2 tumors. That is where we are. We have an exciting set of data coming up in the coming quarters. As a company, we are well capitalized. We have sufficient cash to take us into Q3 next year. We are headquartered in Toronto, about CAD 90 million market cap, CAD 30 million in cash. We generally spend about CAD 4 million-CAD 5 million every quarter with insider ownership of about 22%. We are covered by various analysts, two of them in Canada, two of them in the U.S. In addition to the key advantages that we see with our programs, there are multiple milestones expected over the next two quarters. We will have a full set of expansion data in the monotherapy, which is MDNA-11 on its own.
We'll have completed the entire enrollment in the clinical trial. We'll have top-line data of MDNA-11 in combination with Keytruda. In addition, we'll be looking to partner our Bisoxophers, the GBM program. Finally, we'll be ready with MDNA-113 for IND-enabling studies before the end of this year. Multiple milestones coming up over the next two quarters. I'll stop there. Thank you.
Wonderful. Thank you, Fahar. A few questions for you with the time we have left. First, the AACR is one of the biggest cancer conferences of the year. It just took place a few weeks ago. Talk a little bit about that. What was the general reception like as Medicenna's posters, presentations went off at that conference?
Yeah, it was just quite amazing.
In fact, during the poster session, which lasts about three hours, we were surprised that we did not get a chance to even move away from our posters. There were two of us standing and answering questions. It was pretty much packed around our poster. It was really busy. On the second day, on the last day of the conference, we actually had security ask us to leave because we had so many interested parties wishing to talk to us. We had individuals from sort of the large big pharma come and meet with us, really excited about the data. Really encouraging. We presented data on both MDNA-11, but also our bispecific MDNA-113, where there was a lot of excitement. Yes, very well received. We are keen to share more data in the coming quarters.
Fantastic. All right.
Give our audience about 30 seconds of closing remarks. We are out of time. We have lots of questions for you, Wilson, but 30 seconds of closing remarks for our viewers today.
Yes. Just to let you know that Medicenna has a really exciting pipeline around the immune interleukin space and building a pipeline around bispecifics checkpoint inhibitors. We have multiple data readouts coming up with the intent that these readouts will address the huge unmet needs for patients who do not have therapeutic options, including checkpoint inhibitors, where these patients fail those therapies. We believe MDNA-11, either on its own or in combination, is already demonstrating response rates of 30%-50%, with some patients having really long-term benefit. Look forward to sharing more data. We are excited about the data set.
Hopefully, it puts us in a position where we are open to potentially partnerships, collaborations, et cetera, in the next two quarters. Looking forward to sharing more information with you in the coming year.
Wonderful, Fahar. Thank you for your time today. We hope to see you again real soon.
Thank you. Take care. Bye-bye.
All right, everyone. We'll be right back.