Good afternoon, everyone. I'm Charles Zhu, one of the Senior Biotechnology Analysts at Guggenheim Securities. Thank you all for joining us for our next and last session for today. We are joined by Fahar from Medicenna. Fahar, thank you so much for participating at our conference today. We really appreciate it. Perhaps just to kick us off, could you provide us an overview of your company, platform, and pipeline, please? Yes. Thank you, Charles. Thank you first and foremost for inviting us to be here today. It's always a great event. Very briefly, Medicenna's focus has been essentially around a platform, we call that Superkines. Those Superkines are based on three different interleukins, namely interleukin-2, -4, and -13. These different interleukins have been generated, so there's a whole library of these interleukins where, using a combination of yeast display together with directed evolution, we've just come up with a whole range of different cytokines that can be engineered to be either a superagonist, superantagonist, or anything in between. It allows us to use these different cytokines or interleukins in a number of different kinds of diseases, including oncology, autoimmune disease, and, inflammation, for instance. From a pipeline perspective, there is a lot of promise in terms of what we can build, in terms of what we can generate for different kinds of indications, but of course, the focus at Medicenna is very much around the oncology space. Most of the work that we're doing right now is driven on the oncology side. If you look at the pipeline that we have, first and foremost, the molecule that's our sort of lead candidate is MDNA11. It's recruiting patients in a phase 1/2 clinical trial for solid tumors. It's an IL-2 superagonist. The second program that we have, which is a program that has completed a phase two clinical trial, ready for phase three. It's a molecule called MDNA55 for recurrent glioblastoma. That program has pretty impressive data. We are looking to see a potential partnership for that asset and a company that can take it to the marketplace. We also have earlier stage programs around our Superkines. The great thing about our Superkines is that because they're engineered, they allow us to create fusion proteins. They allow us to fuse it to antibodies, to checkpoints, to other Superkines, cytokines, et cetera. Therefore, we have created what we call BiSKITs or bifunctional superkines for different immunotherapies. Amongst those, we have a molecule which has a fusion of an IL-2 superagonist with an anti-PD-1 checkpoint inhibitor. You've got sort of dual functionality built into one molecule. As such, we have that program still in early or sort of call it late discovery as you optimize and hopefully take that into the IND-enabling studies towards the end of the year. Also around the IL-4, IL-13 space, we have a IL-4, IL-13 superantagonist. We call that MDNA413, where the intent here is to target immunosuppression in the tumor microenvironment by targeting myeloid cells as well as repolarizing the macrophages from the 2A to a M1 macrophage. Make it more inflamed, make a tumor which is generally cold to make it hot so that other immunotherapies can work together. That's essentially where we are. There are other very early programs that we continue to work on, but the focus essentially right now is on MDNA11. Great. I guess, you know, with that MDNA11, it's an IL-2 agonist. Could you perhaps help us understand its mechanism of action as well as how it's potentially differentiated from other IL-2 agonists which frankly have generated underwhelming clinical results? Yes. That's true. This is where we sort of differentiate our platform, our molecule, unlike most others, and this is what we've been able to do with the directed evolution, is create a version of IL-2 that addresses the concerns of Proleukin in all forms possible. First and foremost, we have engineered the IL-2 program in such a way that by inserting five mutations, we have dramatically improved the binding affinity for our IL-2 towards the beta receptor. This way, we're able to mechanistically stimulate the both the adaptive, as well as the sort of the immune system in such a way that can boost both CD8 T cells and NK cells with the beta binding. We have inserted a couple of mutations that allow us to block binding to the alpha domain, this way, not stimulating the Tregs. We have accomplished that with the molecule. We have been able to extend the half-life of the molecule by fusing it to albumin. By doing that, we have a much better half-life of the drug and therefore have seen PD effects with the drug lasting up to two weeks. Finally, by virtue of using albumin as a half-life extender, we are potentially at least seeing in animal studies that albumin tends to accumulate in the tumor. Accumulates into my draining lymph nodes and the lymphatic system. This is sort of a fourth additional characteristic of a molecule that sort of differentiates from every others out there. We have so far seen in the clinical data to date, mechanistically, we have seen boosting of the CD8 T cells, NK cells, but not Tregs. We are seeing the activity as predicted based on the design of the molecule. We are seeing the PD effect last two weeks. Also, we've seen half-life extension by about 30-fold relative to Proleukin. This has enabled us to administer the drug instead of five times or rather three times a day for five days to once every two weeks, and therefore allows us to accomplish a lot of things that Proleukin has had challenges with. Great. Could you also talk about, you know, the perhaps the avoidance of the alpha domain, the superagonism of the beta receptor, and, you know, how maybe some of the other IL-2 agonists in the space have behaved with respect to those similar characteristics? Yeah. I think that's a really good important question. I think if you look back, particularly, if you look at the past 12 months, especially last year, we had a series of announcements where programs in the IL-2 space had to be abandoned or restarted. I think the important aspect is to look at the data from the perspective of the Nektar data, for instance, that was presented at SITC, and clearly showing that, if you go back, I think the thinking was that Nektar was a not alpha IL-2, which we know that it's actually a long-acting Proleukin. By fusing and taking Proleukin as the key molecule and simply PEGylating it, what they did was, yes, they blocked binding to alpha, but they also blocked binding to beta. As the pegs were coming off, you were actually exposing the alpha binding domain equally as you were exposing the beta binding domain. In the end, if you look at the data from the recent Phase three clinical trials, what we saw was what you would normally expect with an IL-2 or a Proleukin where there was a huge increase in the population of Tregs in the tumor, paired biopsies. Whereas if you looked at their CD8 T cell counts and NK cells in the tumor, you could see that there was virtually no change, indicating that having that alpha binding is a liability and therefore has to be avoided, which is what we do with our molecule. From that perspective, I think, we've accomplished that. If you look at the other programs where you, for instance, look at SAR444245 or THOR-707, I think they did an elegant job in blocking binding to CD25. At the same time, they were blocking binding to the beta receptor. Ended up with a molecule that has sort of potentially poorer PD effects of the drug, and therefore having to go back to the drawing board and see how they can change the treatment schedule. What validates our approach further is that if you look at the data from Alkermes' Nemvaleukin molecule, although mediocre data, but nevertheless, way better than what we saw with Nektar in a single-agent setting. They've similarly done a good job in terms of blocking the binding to the CD25 or alpha. Their approach of blocking the alpha binding domain has been such that they haven't interfered with binding to the beta domain, and therefore have retained the Proleukin's beta activity and left that intact. What you see is a decent some signs of activity of the drug in a single-agent setting. We think what we've done with our molecule is remove the ability to bind to alpha. Unlike Alkermes, where they're sort of simply maintaining the Proleukin's binding to beta, we have boosted that by about 30-fold, and therefore are able to more efficiently stimulate the cancer-fighting immune cells, the CD8 and NK cells. Their half-life characteristics are obviously not ideal. They have to administer the drug every day for five days, which is obviously a challenge. In our case, we've been able to extend treatment so that we can treat patients every two weeks. Finally, the sort of the icing on the cake, as you may say, is that we have the albumin portion that allows the drug to accumulate in the tumor as well. I would say that we are highly differentiated. I'm good to see that the data from Nektar, on the one hand is showing that alpha binding is detrimental. Good to show that not binding to alpha through Nemvaleukin's data has potential. I think we think we are on the right track. Great. I guess that's a great segue as well, to the clinical data that you've presented so far. Right. Perhaps could you remind us of the data you have so far as well as your current status, progress, and next development steps? Right. At the moment, we're in the dose escalation portion of the study. The design of the study is that we would conduct a dose escalation part of the study and establish the recommended phase two dose. Subsequent to that, we'll be pursuing a dose expansion in a single-agent setting with looking at two or three different tumor types. Looking at combination with pembro through a collaboration with Merck, and looking at that combination as well. That's basically the overview in terms of the study design itself. So far, we have been encouraged with the safety data to date with the dose escalation that we've done with MDNA11 in a single-agent setting. Starting at three micrograms per kilogram, we've been able to go as far as cohort four at 60 micrograms per kilogram. Just recently, we announced this week that we have cleared cohort number five, which is 90 micrograms per kilogram, and initiated the last phase of the dose escalation to the 120 micrograms per kilogram. What we have done in the study itself is to, in order to mitigate potential safety issues, we've basically, particularly at doses cohort four onwards, started dosing patients in a sort of step-up dosing regimen where we treat patients the first dose at 30, second dose at 30, two weeks apart, and then we get to the target dose of either 60 micrograms, which was the cohort four, or 90 micrograms in cohort five. In cohort six, what we're doing is essentially starting at 30, but instead of repeating 30 again, we are moving on to straight to 60 micrograms per kilogram. That allows us to go into a dose which is already shown encouraging activity of the drug within two weeks instead of waiting for four weeks. That's the plan in terms of the sort of cohort six. The next dose after 60 will be 90 and then 120, okay? That is the plan for the cohort six. We are hoping to share data in the coming weeks, first and foremost. Let me sort of go back and sort of give you an update as to where we are with the data so far. Of the 14 patients that we have treated in the 1st four cohorts, we've seen that five patients had tumor control, meaning stable disease or partial response. That's really encouraging considering that more than half of the patients received a suboptimal dose of less than 60 micrograms. Also that, in a patient with pancreatic cancer, which as you know, is a challenging space to be in, particularly for immune oncology, that particular dataset was unexpected. It was a pleasant surprise to see that the patient who had originally failed the FOLFIRINOX regimen was not able to tolerate the gemcitabine/Abraxane combination, was not responding to KEYTRUDA. That patient entered the study at the 1st scan showed stable disease. Second scan, we had a unconfirmed PR, and subsequent to that, a confirmed PR. The trend was that the response in that patient was continuing to deepen. Encouraged with that particular patient. Also, in melanoma patient, where the patient has gradually escalated from 10 to now 60 micrograms per kilogram, that patient remains on study now for over a year, and again, showing tumor control, which is again, very encouraging in a patient that had failed both radiation, chemo, and checkpoints as well. Based on that early efficacy data, we're really excited with what we have seen so far. If you look at our dosing, if you were to look at, you know, comparing our dose on an IL-2 equivalency basis to, let's say, Nektar's dose, which was just six micrograms per kilogram, we've now in the 120 micrograms are at four times higher dose than a molecule that was less potent, considering that our molecule is a lot more potent than Nektar's molecule. However, it's very specific for the beta domain. The frequency of administration is more frequent than Nektar's administration, which was every three weeks versus ours, which is every two weeks. We're seeing a really good safety profile so far. We're happy with that, and encouraging signs of clinical activity already in the dose escalation portion. Great. I guess, you know, with this dose escalation data coming out, you know, what are your thoughts around tackling the dose expansion cohorts? Right. Do you think you can expand that to cohort five? Will you wait for six? Which two tumor types? How are you thinking about that? That again, you know, obviously we've seen really promising data already in cohort four at 60 micrograms per kilogram. We've not seen any DLTs in cohort six, where we haven't seen any dose deescalations or, we've not seen dose discontinuations, et cetera, in half the patients or any patients withdrawn from the study because of safety issues. We now have a choice of 60 and 90, and potentially if 120 works out as well, then we've got three doses to pick from. In the end, it's gonna be the safety review committee and what we look at the PD data from not only the previous cohorts, but also the cohort five and six, and compare those and see what might be the best dose to pursue within the context of not only activity, but also safety of these patients. We hope to make that determination next quarter that will help us with then initiating the dose expansion phase of the study. Unlike the dose escalation portion where we've been enrolling patients who are really end-stage patients, we have a wide variety of patients that we can enroll, as many as 12 or more different tumor types. In the dose expansion phase of the study, we intend to enroll patients who have fewer treatment regimens, who are healthier, but at the same time narrowing it down to just perhaps two or three tumor types in 40 patients. We have, on average, about 15 patients per group. One of the groups is definitely going to be melanoma because that gives us a reference point relative to Proleukin, and therefore gives us a context as to how does our drug perform relative to Proleukin in that melanoma patient population. With regard to potentially one or two other cohorts within the dose expansion, we are conducting an extensive review analysis with two dozen KOLs that have been interviewed by a third-party vendor to essentially get their feedback based on data we have presented so far with MDNA11 to them and the safety profile and get their feedback as to which ones would perhaps be the best ones to select for the dose expansion phase. In addition to melanoma, there'll be two more types. We haven't determined that, but we will in the next quarter. In the next quarter, we will also provide efficacy results from cohort five. We'll have scans for all of those patients and potentially cohort six as well. lots of new data to present in the second quarter of this year in addition to identifying the recommended phase two dose, the patient population, et cetera. Before the end of this quarter, we will provide more light on PK/PD data from our cohort five in addition to follow-ups or efficacy data from previous cohorts as well. Great. Looking back at some of your, PD and dose response data, it does seem like you do have, you know, a dose-dependent and somewhat dramatic increase in lymphocyte count. Yes. From, let's say, cohorts three, four, and I guess we'll see five. Yes. F rom that perspective, you know, like how should we think about. It does sound like will have more even in cohort six, potentially. Yes. How should we think about any potential association or correlation of that type of a PD effect relative to, you know, potential efficacy or anti-tumor response? It's probably I would say if you, if you look at it within the context of Proleukin data in the past that was published, and I think if you look at it from that perspective, what we have observed is that, with increased lymphocyte counts post-treatment or even, you know, selecting patients that had higher lymphocyte counts, we saw that from Proleukin's data, the patients that had higher lymphocyte counts at the baseline, had better outcomes. In our case, we thought, well, let's amend the protocol so that in cohort four, five, and six, that we would only enroll patients with baseline lymphocyte counts above 1,000. That we have done, but in retrospect, when we look at the data we have, for instance, the pancreatic cancer patient that responded had a baseline lymphocyte count above 1,000, whereas the patient that is the melanoma patient had started in the study with a baseline lymphocyte count of just 600, and that patient continues to benefit. What we saw is that over a period of time, the baseline lymphocyte count in these patients, whenever it came back to baseline, the baseline always increased. We've got to a stage where the melanoma patient started the study with 500-600 lymphocytes per microliter, but now is well above 1,000 after the 5th or 6th dose. Does that, you know, is it relevant for us or not? I think as long as the patient stays long enough in the study, there is an opportunity for patients to benefit from the therapy. Maybe it's with our molecule being so crucial in the sense that its activity is driving CD8 and NK cell proliferation so much more effectively. Perhaps that's not relevant. At least, you know, we are collecting the data. Great. I guess, you know, how are you thinking about execution, and how are you tracking towards, you know, KEYTRUDA combination studies, as well as results? The planning is that, you know, we would identify the sort of, again, the three cohorts in the combination setting as well. We'll obviously work together with Merck in identifying which ones are the best ones to proceed, but we haven't, of course, determined what we need to do in the monotherapy setting. That will pretty much drive what we plan to do with the combination setting. First and foremost, we'll have to establish the combination dose with KEYTRUDA. We'll probably go one or two dose levels below our RP2 dose and then proceed with that and have some data at least from the dose escalation portion with KEYTRUDA combination, perhaps by the end of the year. That's the plan. With respect to the monotherapy dose expansion, we should see initial data at the end of Q3 with more fulsome data in Q4. Great. Perhaps just to close out, could you remind us of your cash balance as well as expected runway relative to upcoming milestones? Yeah. As of our last quarter, we had in Canadian dollars, CAD 36 million. That basically allows us to take the programs to all the key milestones that I just talked about and essentially takes us all the way to the middle of next year. The next, overall, about 18 months of cash, we burn about CAD 6 million a quarter. That takes us to that point where we will have a full set of data from the single-agent monotherapy and early sets of data on the combination arm as well. Allow us to complete the ABILITY Study. It will allow us to identify the lead candidate with our BiSKITs platform and hopefully find another new candidate that we would take further along with respect to the IL-4/IL-13 space as well. Great. Thank you. With that, we'll wrap up. I wanted to say, Fahar, thank you very much for joining us here today. We really appreciated your participation. Please enjoy the rest of your day. Sure. Thank you. All right. Thanks.