Hello. Hey, guys. Thanks a lot. We hope that you're having a great time today. Up next, we have Fahar Merchant, President and CEO of Medicenna Therapeutics. Fahar, over to you. Can you hear me? You can. Okay, great. So, first and foremost, obviously, I'd like to thank Bloom Burton for inviting us today to present. I'm glad that we had another opportunity today to provide you all an update on Medicenna. So just to put a note here that I will be making forward-looking statements, so I encourage you to look at our public filings. So very quickly, what is Medicenna and where we are? We are, first and foremost, to let you know, we are a publicly listed company on the TSX, symbol MDNA. We are really focused in the immunotherapy space, primarily in the oncology space at the moment. And we have two really exciting assets that I'll talk to you about, today, both clinical assets. The first one is MDNA11, currently enrolling patients in phase I/II clinical trials in a variety of different solid tumors. These are all advanced solid tumors. The second program I'll talk to you about is some additional evolution that's going on with our program with bizaxofusp, formerly known as MDNA55. This is a drug for treating patients with recurrent GBM, recurrent glioblastoma, and this particular program is essentially phase III ready. We've got two really exciting early and late-stage assets in our clinical pipeline. To add to our pipeline, we have really novel pipeline-in-a-product opportunities for not only cancer, but also autoimmune disease, inflammation, neuromuscular diseases, et cetera. All of these come through by virtue of the assets that we have, which are around what we call the Superkine assets. I'll talk to you about that shortly. The company is expecting a number of key milestones over the next three quarters. Before the end of this quarter, we'll provide some additional data on our monotherapy expansion with MDNA11, and preliminary data with our Keytruda combination with MDNA11, which will further mature towards the end of the year. With bizaxofusp, we are hoping to secure breakthrough therapy designation for this drug, as well as get alignment with the European Medicines Agency on the design of the phase III clinical trial, and of course, also looking at a partnership for this program, which is now phase III ready. So we have a number of milestones coming up. These milestones are funded. We have just over $20 million in cash that keeps us going to get to the key milestones in the coming quarters. So let's talk first and foremost about our platform. The platform, as I said, is based on the Superkine platform, assets that we've in-licensed from the Center for Biologics at the FDA, as well as these next-generation Superkines, which we've in-licensed from Chris Garcia's lab at Stanford University. Really focused on three cytokines: interleukin two, interleukin four, and interleukin thirteen. So what are these cytokines? These cytokines are really proteins, molecules that we all have that help us in modulating our immune system. So we could boost the immune system to a stage where these immune cells can be activated, particularly in situations where you want to fight cancer, for instance, or infectious disease. So that's where you need to really have these cytokines become super cytokines or super agonists, and that's why we call them Superkines. So using this technique at Stanford, using a technique known as directed evolution, which was part of the 2018 Nobel Prize, what we have been able to develop is a range of cytokines or Superkines that are either super agonists or super antagonists. And you would need super antagonists in situations where your immune system is far too active, in patients that might have autoimmune disease, inflammation, et cetera, where you want to calm the immune system down. So we have this multiple pipeline-in-a-product opportunities with our Superkine platform. I'll talk to you about these later on very briefly. So looking at our pipeline, you can see the first three bars refer to our GBM, which is phase III ready asset. We have a single agent monotherapy study going on with MDNA11 in a phase II expansion study, and just recently commenced a combination with a sort of a clinical trial collaboration with Merck, where we are combining our MDNA11 with Keytruda, and then, of course, the earlier stage pipeline that we'll briefly talk about later on. Okay? So let's start MDNA11. This is a program that's currently enrolling patients. It's an IL-2 super agonist. I'll tell you a bit more about what this is all about. So let's talk about MDNA11 and IL-2 specifically, okay? So IL-2 has been a drug that has been approved or was approved, in the 1990s, for treatment of patients with melanoma, as well as, kidney cancer. However, this particular drug has had limited clinical use. This drug, mostly as a result of the toxicity issues with this particular molecule, this drug was being administered, and even today, administered to patients who are relatively healthy, but the treatment has to occur in an intensive care unit because the drug itself could kill the patient. So there is, with this drug, indications about 15% of patients will respond to treatment, and about half of those could have long-term cures, which is really intriguing if you can achieve that, but with a safer drug. The other thing about this drug is that it is relatively small. That means it clears through the kidneys very quickly. Patients have to get this drug every eight hours for five days in an intensive care unit. So obviously, something that's not taken off. This drug is currently marketed by Iovance, and the reason Iovance purchased this drug for about $250 million was simply that they can use it for the TILs-based programs or cell-based therapies, because these cell-based therapies need IL-2 to grow, and once you inject the cell therapy in the patient, you need IL-2 to continue to perpetuate those newly infused T cells. But as you can see, challenges there. So what did we do with MDNA11 that is quite unique? First and foremost, you know, we're seeing some really exciting data. We've seen already responses, single agent responses. Four patients out of 14 have responded to therapy. We have had a couple of patients, one with pancreatic cancer and melanoma, where the target lesions have completely disappeared, and we've seen a desirable safety profile. The patients don't, are not treated in an intensive care unit. They are... These patients also are dosed once every two weeks. So this is the key sort of advantages of what we have with MDNA11. So how were we able to achieve these unique characteristics of MDNA11? Mainly by sort of engineering the molecule by placing very specific mutations or by using directed evolution. What we have is, if you look at the IL-2 on the sort of the extreme left for you, is that we've got two mutations that pretty much block binding to a receptor on immune cells called the alpha receptor. The alpha receptor is responsible for the toxicity. The alpha receptor is also responsible for actually boosting the population of what we call regulatory T cells. These are immunosuppressive T cells, and therefore, they actually end up protecting the tumor, so you don't want that to happen. And that's why we've knocked down, we've inserted two mutations, so binding to alpha is abolished to improve safety and not promote T-reg proliferation. The other thing that's happened is we've inserted five mutations that dramatically increase the affinity of the molecule towards cancer-fighting immune cells. So these are your CD8 T cells, your natural killer cells. These express predominantly what is known as the beta-gamma receptor, and this molecule has been engineered so that its affinity for the beta-gamma receptor has been increased by about a hundredfold relative to the old Proleukin drug. So therefore, you end up using a lot less of the drug, but selectively boost the population of your cancer-fighting immune cells. So what we find is we boost the population of effective immune cells, we improve the memory response, and the other thing that's quite interesting is that you also reduce or prevent exhaustion of your cancer-fighting natural killer cells. So a lot of these things that really help. And then finally, the big issue with Proleukin was administering the drug 3 times a day for 5 days. And to avoid that, what we've done is fuse the molecule with albumin. So now the molecule is much larger, stays in your bloodstream much longer, and therefore, you're now increasing the half-life of the drug, so you're now being able to administer the drug once every 2 weeks instead of 3 times a day. Okay? And then finally, the unique thing about albumin is that it tends to accumulate in the tumor and in the tumor-draining lymph nodes. So these are sort of key benefits of this drug, and we believe that approach has us differentiated from all other IL-2 programs that are in the clinic. So going back to the design of the study, you can see the top is essentially we first started the dose escalation portion of the trial. We've established the recommended dose for expansion, which is 90 micrograms per kilogram. We are currently enrolling patients in a monotherapy dose expansion, looking at three different tumor types, patients with melanoma, non-melanoma skin cancer, and also patients with a biomarker known as MSI-High tumors. So that's currently underway. The second portion of the trial, which is the combination with Keytruda, that program has just started enrolling patients. We again here doing some initial dose escalation. We have not identified all the tumor types that we'll be looking at, but suffice it to say that just to give a bit of background, Keytruda today is the world's biggest-selling drug, annual sales of $25 billion a year and growing, okay? We believe that a drug such as MDNA11 could potentially be a prerequisite for further improving outcomes for patients that are currently receiving Keytruda. Remember, only a third of the patients that get Keytruda or checkpoint inhibitors respond to treatment. The remaining two-thirds do not. We believe that this approach of combining MDNA11 with Keytruda would substantially increase the patient population that would benefit, early on when the patients enter a study or when they're first diagnosed. In any case, the drug that we've used, MDNA11 so far, is obviously in patients that have failed checkpoint inhibitors. What we have seen from a safety profile is rather, you know, a desirable safety profile, been quite mild. Essentially what we have is we've not seen any DLTs, we have not seen any grade 4 or greater events. Most of the events have been grade 1 and 2, most of them have been very transient. Okay? But really exciting is the recent data that we've seen here is the efficacy data so far. If we look at a multiple number of IL-2 programs that have been in the clinic for the past 5 years, Nektar in collaboration with Bristol Myers Squibb, which was a $3.6 billion transaction. You had Sanofi acquiring Synthorx with their IL-2 program at $2.5 billion just for that one drug. Both of those programs have been abandoned because they were not able to see even one patient responding to the treatment. Here we have data on 14 patients, and out of those 14 patients, we've seen 4 responding to treatment, of which 2 have had complete regression of their target lesions during this study. So really excited about the data so far. We've seen durability in the sense even patients that have stable disease, have stable disease beyond 6 months, including one patient that has stable disease for a year and a half. So if you look at these individual patients, I'd like to point out to the fact that we have, as I said, 4 partial responses, 2 patients, one of them a pancreatic cancer patient. So as I said earlier, Proleukin was approved for melanoma and kidney cancer. There was no prior history that a drug such as interleukin-2 would help patients with pancreatic cancer, and we're seeing a patient there that has a complete regression of the target and also non-target lesions. And, more recently, we've seen a patient with melanoma has also received, has achieved complete regression of the target lesions. So encouraging, although early with just 14 patients, but really trending in the direction that we are really excited to see. So in summary, as I said, four partial responses, response rates well above what you see with Proleukin, with a toxic dosing regimen at about 29%, with a 50% clinical benefit rate. We have seen a safe profile of the drug, treatment every two weeks. And finally, I would say, based on all the competitive space in the IL-2, we easily, easily say that we're probably a leading IL-2 program in the clinic at this moment. Okay? The key milestones coming up in the first half of this year, which is before the end of this quarter, is additional monotherapy expansion data. We'll have initial combination data from the combination with Keytruda, and then in the second half of this year, we'll have top-line data for monotherapy and preliminary efficacy data with combination with Keytruda. Okay? So moving on to our second program. This is our phase III ready program, MDNA55, or bizaxofusp. This is for patients with recurrent GBM. This is a drug that has received Orphan Drug Designation, Fast Track Designation, and we're looking to secure Breakthrough Therapy Designation with this drug. Okay? So just as a bit of a background on glioblastoma, as we all might be aware, this is a uniformly fatal kind of brain cancer. This is nothing out there has been available for patients over the past three decades. There's been temozolomide approved in sort of the early 1990s, but since then, there has been nothing for these patients. And there is a huge unmet need, particularly in patients who have recurrent disease, who've had surgery, radiation, chemotherapy, and the tumor is now too deep in the brain to conduct additional surgery, and therefore, these are sort of your end-stage patients. So here we are using the drug, MDNA55, or bizaxofusp. I'll talk to you about that drug. We've seen some compelling results. I'll share those data with you shortly. This program is essentially phase III ready, and the market opportunity with this drug is quite considerable, as you can see, not only for recurrent GBM, but when we expand it into other CNS tumors, you can see the market opportunity here, quite large, at about $4 billion with this drug. What is bizaxofusp or MDNA55? It's essentially a interleukin-4 that has been fused or linked to a toxin. By doing that, what we are able to do is target glioblastoma tumors that express the interleukin-4 receptor. Patients express the IL-4 receptor in GBM, so what happens is the drug binds to the IL-4 receptor on the tumor, delivers the toxin, and causes cell death. This drug is administered just once, okay? It's a one-time intratumoral administration. This is done by neurosurgeons, typically using the same procedure they normally use for brain tumor biopsies. So using the same approach, they place the catheter in the tumor, infuse the patient for a day, and that's it. Okay? And And what we've seen with this data is quite impressive. We've seen that we've been able to double the median survival of patients receiving a single treatment in end-stage patients that are not surgically resectable. And we've seen here that, with respect to if you look at just one-year survival, we've increased the one-year survival by 250% and over 100%, the two-year survival. We did this by actually enrolling patients in a separate study, where we enroll patients that met the same inclusion, exclusion criteria that we did in our clinical trial, and we matched them based on those inclusion, exclusion criteria. You can see that we've been able to demonstrate patients with current treatments available, median survival is just 7 months, versus nearly 15 months. We went with this data to the FDA, and we were able to convince the FDA that we need to conduct this clinical trial in such a way that the majority of patients get the drug. They're not put in a control arm as much as we possibly can. This was the first time ever the FDA approved a pivotal study design, where the majority of patients will receive our drug, okay? The majority of patients in the control arm recruited from a hospital database. That allows us to then not having to unnecessarily put pressure into patients to take a drug that does not work. We were able to achieve that, and that's the plan for the phase 3 trial. Our plan is to secure essentially approval from the Europeans as well to approve that design. From the market perspective, as I mentioned, this huge market opportunity, $800 million for the first indication, but we expand into first-line patients, that increases to about $1.4 billion, and then finally into patients that have brain metastases. Again, that sort of raises the market opportunity to about $4 billion. In addition to these two really exciting clinical assets that we have an exciting portfolio of preclinical assets, and these are addressing not only cancer, but also outside of cancer, in areas where there have been a number of transactions. So here, first and foremost, we have a bifunctional Superkine, an interleukin two, which is the same one as we use in our MDNA11 program, and a checkpoint inhibitor, an anti-PD-1. So two activities fused together in a single molecule. As you know, the patents on checkpoint inhibitors are expiring in 2027, 2028. We believe this is a much better way of addressing this unmet need by delivering two drugs at the same time. We've seen a recent preclinical transaction where Roche purchased Good Therapeutics for $250 million, despite the fact the program was only in preclinical and is still in preclinical development. The unique thing about our drug is that it is a bifunctional drug. It's conditionally activated at the tumor site, but unlike anybody else, we deliver the drug to tumors that express the IL-13 receptor alpha 2, which is found in about 2 million cancer patients every year. The opportunity here is massive. Then there is another area which is the overactive immune system, where we want to calm down the immune system by blocking activity of IL-2 and IL-15. This is very relevant in autoimmune disease, multiple sclerosis, arthritis, et cetera. And here, as an example, you see a recent transaction where Novartis acquired Calypso, again, preclinical asset for $450 million. Then finally, we have an IL-4, IL-13 antagonist, and this IL-4, IL-13 antagonist really is, we think, a much better option than Sanofi's drug, Dupixent. Dupixent today is Sanofi's largest-selling drug, selling about just over $11 billion in sales annually for treating patients with atopic dermatitis or eczema and asthma and so on and so forth. The unique thing about our drug is that it is much more specific, much more targeted, and because it's smaller, you can administer the drug systemically or by aerosolized version, so nasal administration. So we think this drug has a much better potential targeting, safety features, and use for the patients. Finally, we've got a number of catalysts coming up. I won't go through the whole list, but suffice it to say that in addition to data on MDNA11, we'll have updates in 55 over the next 2-3 quarters, and there are, of course, multiple conferences that we intend to present or expect to present in the coming quarters as well. So in the end, to summarize, the company has two very exciting programs addressing huge unmet needs in oncology. First and foremost, we believe the IL-2 program is potentially a key component that will work together with checkpoints, and then, of course, addressing glioblastoma, which is not being addressed for the past three decades. The company has just over $21 million in cash, enough to take us through to Q2 of next year. Market cap, about CAD 132 million. About 24% of the stock is owned by insiders. So with that, I'll end. Happy to answer any questions if you have. Thank you. We have a bunch of mics around, so please, sorry. In the combination with Keytruda? Yes. Who owns the IP for that? Of course, Merck owns the IP on that program, but we have filed a patent where the combination of MDNA11 with any checkpoint inhibitor is something that we've filed separately. Okay? And the patent on the BiSKITs, which is the bifunctional Superkine, that's also Medicenna's. Okay. You talked about the existing checkpoint inhibitor patents expiring in 2027. What would be the current sales of checkpoint inhibitors and people who own a big bundle of them that might end up being interested in working with you? Or does your deal with Keytruda perfectly prevent that, dealing with other people? Yeah. So there are other companies that are developing checkpoints that have marketed products in the checkpoint space, Keytruda being one of them, which is a Merck product. There's Opdivo, which is a Bristol Myers product. There the sales are about $10-$12 billion. And there are others, you know, who, you know, also have checkpoint inhibitors, anti-PD-1s, that again, probably add another $5 billion-$10 billion in sales. So we are definitely well above $30 billion in sales with checkpoint inhibitors currently, and therefore, we're sort of not restricted to just work with Keytruda. We, the collaboration allows us to, you know, allows us to proceed with transactions with any other company. Okay? Sorry, there's a big intra-individual response to cytokines. Right. Right here. Sorry, where are you? Oh, there. Okay. The question I have is, what are you doing to optimize your protocols for these individuals? In terms of, I missed the first sentence. There's a big intra-individual response to cytokines. Right. So, you know, clearly, you know, when you're treating patients who are end-stage patients, you get a very heterogeneous population in the sense that they have received multiple therapies or different kind of therapies, and of course, tumor types that are different from one patient to the next. So the intent, of course, as you try and—what we first and foremost, I have to say, is that we're seeing this durability that's not been seen before, and very consistent with what we've seen before with Proleukin, earlier on, where tumors that eventually have complete responses have shown to be curative in some patients. Okay, now, the question is: Can we accomplish that down the road? We don't know, but I think if we are able to take this program into earlier stage, patients that are newly diagnosed or in combination with checkpoint inhibitors, I think there'll be a better chance for the durability of the treatment. But also we, you know, we are collecting a lot of data from the pharmacodynamics, collecting data from patient samples as well. It'll give us an idea as to what patients are responding to treatment and what patients are not, and this way, we'll be able to sort of narrow it down and be, hopefully down the road, be selective in treating patients that, are likely to respond with this, this therapy. Okay? All right. Yeah. Thank you.