Hello, and welcome to the Medicenna Therapeutics MDNA11 clinical trial update call. All participants are now in listen-only mode. There will be a Q&A session at the end of the pre-prepared remarks. Please be advised this call is being recorded at the company's request. I would now like to turn the call over to Alexander Morin of Russo Partners. Please go ahead. Thank you, operator, and thank you all for participating in today's conference call. This morning, Medicenna issued a press release providing an update on its MDNA11 clinical trial. If you have not seen yet the press release, it is available on the investor page of Medicenna's website. Before we begin, I would like to remind you that certain statements and information shared during this call constitute forward-looking information within the meaning of applicable securities laws. All statements, other than statements of historical facts shared during this call and that relate to the future operations of the company and other statements that are not historical facts, including statements related to the clinical potential and development of MDNA11, preliminary clinical data, cash runway, and the presentation of additional data and other milestones, are forward-looking statements that are subject to risks and uncertainties. There can be no assurance that such statements will prove to be accurate. Actual results and future events could differ materially from those anticipated in such statements. Important factors that may cause actual results to differ materially from the company's expectations include the risks detailed in the annual information form, management discussion and analysis, and Form 20-F of the company, and in other filings made by the company with the applicable securities regulators from time to time in Canada and the United States. Listeners are cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the company. You are cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect, and actual results may differ materially from those anticipated. Forward-looking statements contained in this conference call are expressly qualified by this cautionary statement. Except as required by law, the company does not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements, only as expressly required by Canadian and United States securities law. Speaking on today's call will be Medicenna's President and Chief Executive Officer, Dr. Fahar Merchant; and Chair of Medicenna's Development Advisory Committee, Dr. Arash Yavari. I will now turn the call over to Fahar to begin. Fahar? Thank you. The purpose of this call is to provide a summary of the recently completed phase 1 dose escalation portion of the ABILITY study. I'm pleased to say that Dr. Arash Yavari, chair of our Development Advisory Committee, is with us to share this data with you all. Dr. Arash Yavari, a physician-scientist based at the Radcliffe Department of Medicine, University of Oxford, has been working very closely with Medicenna and our MDNA11 program for the past two and a half years. Before I pass this along to Arash, let me provide you all with a little introduction to how MDNA11 is differentiated with respect to other IL-2s in clinical development. As we all know, IL-2 therapy, commonly known as Proleukin, was the first ever immunotherapy approved for the treatment of cancer, specifically metastatic melanoma and kidney cancer. However, due to its severe toxicity, which were at times life-threatening, Proleukin's use was limited to only expert cancer centers that specialized in its administration. Due to its small size, Proleukin is also cleared very rapidly by the kidneys, requiring patients to be treated every eight hours for up to five days for each treatment cycle. Finally, Proleukin preferentially boosts cancer-protecting immune cells, such as regulatory T cells or Tregs, rather than stimulating cancer-fighting immune cells such as CD8 T cells and natural killer cells. The cartoon in slide four shows the design of MDNA11. It comprises of two parts. The green bar represents the engineered IL-2 superkine, which has seven key mutations. Two of them are designed to block binding to the alpha receptor and therefore prevents the IL-2 superkine from stimulating cancer-protecting immune cells, called Tregs, and also reduce the toxicity associated with IL-2. The remaining five mutations dramatically increase the binding of the IL-2 superkine to the beta receptor, which is found on cancer-fighting immune cells, namely CD8 T cells and NK cells. The purple bar is a recombinant human albumin, which serves two functions. First, it increases the size and therefore increases the half-life of MDNA11 by at least 20-fold when compared to Proleukin, allowing us to treat patients every two weeks instead of every eight hours. Secondly, our giving tends to accumulate at the tumor and tumor-draining lymph nodes, which is the site where the immune cells get trained and are activated. In the end, MDNA11 has many features that are distinct from those of other IL-2 programs and has potentially best-in-class features. We have seen these unique features in our animal studies and are also beginning to see those benefits reflected in the clinical setting. As Arash will elaborate, we have already observed encouraging signs of single-agent activity of MDNA11 in pancreatic cancer, one of the most aggressive tumors that normally does not respond to IL-2. The tumor shrinkage continues to deepen, at the most recent scan, the sum of diameters of target lesions had reduced now by nearly 80%, of which one target lesion and one non-target lesion have both completely regressed. While phase I oncology studies are primarily designed to evaluate safety, pharmacodynamics, and pharmacokinetics of a new drug, such as MDNA11, in patients with advanced cancer, we are happy to say that the ABILITY trial of MDNA11 has demonstrated early signs of clinical activity and efficacy, along with a manageable safety profile during the dose escalation portion of the study. We are excited to now advance MDNA11 to the dose expansion phase of the ABILITY study, starting first with the monotherapy expansion, followed by its combination with KEYTRUDA in Q4 of this calendar year. In the monotherapy dose expansion portion of the study, we will implement the recommended dose for expansion, as well as focus on tumor types that are more likely to benefit from immunotherapy with MDNA11. I will now have Dr. Yavari present the results of the phase I monotherapy dose escalation portion of the study. Arash? Thank you, Fahar, and thank you to all those listening. ABILITY is a first-in-human, open-label, phase I/II study of MDNA11, a next-generation, beta-only, long-acting IL-2 superagonist in patients with advanced solid tumors. The primary objectives of the monotherapy dose escalation phase are to evaluate the safety and tolerability of MDNA11. This, in conjunction with data on the pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of MDNA11, informs selection of a recommended dose for expansion, RDE, for further evaluation during the dose expansion portion of the trial in selected tumor types. To date, six dose levels of MDNA11 have been evaluated in monotherapy dose escalation, with the most recent cohort evaluating a target dose of 120 mcg per kg MDNA11, given intravenously once every two weeks. Patients enrolled to monotherapy dose escalation have had a range of advanced solid tumors, with the majority treated with multiple lines of systemic anticancer therapy. This included prior use of immunotherapy in three-quarters of patients. The single-agent adverse event profile of MDNA11 in dose escalation shows it to be generally well tolerated to date, with the majority of AEs of low grade and transient in nature. No protocol-defined dose-limiting toxicity or Grade 4 or Grade 5 adverse events have been reported. Turning to the pharmacodynamic data, MDNA11 induces a prolonged dose-dependent expansion of lymphocytes in the peripheral blood, indicated by the increase in absolute lymphocyte count. Lymphocytes include CD8- positive T cells and NK cells, which are the antitumor cellular effectors of IL-2-based therapies. Of note, in this regard, induction of high lymphocyte counts has been shown to correlate with response to Proleukin. This induction of lymphocyte expansion is seen to be sustained over multiple cycles of administration and across a range of pretreatment lymphocyte counts. High blood eosinophil counts are associated with vascular leak syndrome, which is one of Proleukin's most serious potential side effects. MDNA11 administration was not accompanied by significant stimulation of eosinophils. MDNA11 administration resulted in a dose-dependent expansion of CD8- positive T cells. These are key effectors of the body's anticancer immune response, together with minimal to limited proliferation of regulatory T cells, known as Tregs, which can act to suppress antitumor immunity. This resulted in an increased blood CD8- positive T to Treg ratio, consistent with overall immunoactivation, validating the molecular design of MDNA11. Examining the functional impact of MDNA11 on T cell activation state shows an increased frequency of activated and co-stimulated ICOS-positive, CD8-positive T cells, more prominent for the 90 mcg per kg target dose. Only limited expansion of Tregs expressing the inducible T cell co-stimulator ICOS was observed. ICOS-positive Tregs are immunosuppressive, markedly expanded in response to treatment with Proleukin, and have been linked to worse clinical outcomes. MDNA11 administration was associated with an expansion in OX40-expressing CD8-positive T cells. OX40 signaling can promote the clonal expansion and survival of antitumor effector CD8-positive T cells. MDNA11 use was also associated with an upregulation of OX40-expressing Tregs. OX40 signaling can block the activity of Tregs. This was again most apparent for patients treated with the 90 mcg per kg dose of MDNA11. Examining the swimmer's plots at this early stage of the trial shows encouraging signs of single-agent activity with durable tumor control. This includes a patient with stage four malignant melanoma with pulmonary and mediastinal metastases enrolled to cohort two, who had received two lines of immunotherapy and most recently progressed on nivolumab, an anti-PD-1 agent. The patient was enrolled to the ABILITY trial, underwent progressive intra-patient dose escalation, and experienced stable disease on treatment with MDNA11 for approximately 18 months. In addition, a 55-year-old patient with stage four pancreatic cancer with hepatic metastases enrolled during the dose escalation phase, has shown a durable partial response to MDNA11 at a dose of 60 mcg per kg intravenously, given every other week. The patient had undergone prior complex resective surgery for the cancer, known as a pancreaticoduodenectomy or Whipple procedure, followed by adjuvant chemotherapy with FOLFIRINOX. Unfortunately, there was evidence of disease recurrence, which was treated with two further lines of systemic therapy, including immunotherapy, with continued disease progression. The patient was enrolled to dose escalation cohort four and experienced a confirmed partial response. The cross-sectional CT images of the abdomen show the liver metastases at baseline before treatment in the upper panels, and after treatment with MDNA11 in the lower panels, consistent with deepening reduction in multiple hepatic lesions. The patient continues to receive treatment. This response to MDNA11 is encouraging, given the highly aggressive nature of pancreatic cancer and the absence of response of this tumor type to IL-2-based therapies. Based on the totality of the dose escalation data, 90 mcg per kg given every other week, has been selected as the recommended dose for expansion for further evaluation in monotherapy expansion. This, together with the preliminary findings highlighting the potential for MDNA11 to achieve durable responses in patients with treatment-refractory metastatic cancer, support the opening of the monotherapy expansion portion of ABILITY. This next phase will build on the findings obtained in dose escalation to assess MDNA11's antitumor efficacy in selected advanced solid tumors in the anti-PD-1 failed setting, specifically melanoma, a range of non-melanoma skin cancers, and those with microsatellite instability. In parallel, supported by the favorable single-agent safety profile of MDNA11 observed to date, work is underway to initiate the combination phase of ABILITY. This is designed to evaluate the safety, tolerability, PD, and antitumor efficacy of MDNA11 in combination with the PD-1 checkpoint inhibitor, KEYTRUDA, supported by a clinical collaboration with Merck. With that, we will now move on to some concluding remarks from Fahar before beginning the Q&A session. Thank you, Arash. When looking at how ABILITY's data have matured over time, we have also notably seen evidence suggesting durable anticancer activity with MDNA11 monotherapy, administered via IV infusion once every two weeks. This has come from the aforementioned pancreatic cancer patients, as we see continued deepening of tumor reduction over each of their scans, leading up to 80% reduction in tumor burden. Additional evidence of durability comes from the metastatic melanoma patient, achieving tumor control for over 18 months. Collectively, these antitumor activity data from the ABILITY trial provides a robust demonstration of MDNA11's single-agent potential in advanced solid tumors unresponsive to established treatments. Adding to our enthusiasm for these results are the trial's pharmacodynamic data, which provide a mechanistic rationale for MDNA11's potent antitumor activity while underscoring its best-in-class potential. These results show MDNA11 driving multifold increases in anticancer immune cells. Moreover, MDNA11 has not been shown to stimulate pro-tumor immune cells or eosinophils, which are linked to serious side effects. These favorable pharmacodynamic results are as a result of MDNA11's unique profile, which fuels our belief that MDNA11 has the potential to become a best-in-class IL-2. This hypothesis is already being borne out by the maturing ABILITY study data. We are encouraged with the clinical data to date and look forward to the dose expansion portion of the trial, where the emphasis will be to demonstrate clinical activity and safety in a single agent and later in a combination setting. We plan to present additional data from results of the clinical trial at different conferences this year. We also expect to start enrolling patients in the monotherapy dose escalation arm imminently, with a combination portion commencing in Q4. Early results from the dose expansion will be provided in Q4, and combination data will begin to emerge in Q1 2024. We therefore expect multiple opportunities to share data over the coming quarters, including updates on our BiSKITs program. Our cash runway extends through calendar Q3 2024, well before the key data readouts from the ABILITY trial. By generating additional evidence of MDNA11's antitumor activity in key indications at the recommended dose for expansion, doing the monotherapy and subsequently in combination with KEYTRUDA, has the potential of advancing the company's progress to key value inflection points. In closing, I'd like to stress the significance of our recent accomplishments and reiterate my enthusiasm for the future of our MDNA11 program. With that, I would like to extend my thanks to all those who helped us reach this point, including our employees, investigators, shareholders, and clinical trial participants. We will now open the lines for questions. Operator? Your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we'll pause momentarily to assemble our roster. Our first question will come from Matt Biegler with OpCo. You may now go ahead. Hey, guys. Good morning. Thanks for this data update and congrats on, on moving on to dose expansion. Fahar, could, could maybe just walk us through what gives you confidence that you found the recommended phase II dose? And you can talk a little bit about the pharmacodynamic data. Was it plateauing T-cell responses or target engagement? You know, obviously selection of that recommended phase II dose is a really critical part of this program and something in, in hindsight, I think people criticize Nektar and Bristol for, so any comments you have there would be great. Yes, I'll try to answer your question. Thank you, Matt, for your call and I'll have Arash help me out. First and foremost, I think if we look at the slide deck, I'm not sure if we can sort of share that with you on the call right now, but suffice it to say that from the PD data perspective, what we did see across the board with different parameters that we were looking at with respect to the PD markers. What we found is with the 90 mcg per kg dose, we found that the CD8 to Treg ratio was much greater than that at 60 and 120. We also found that the expansion of very specific CD25- positive cells, the ICOS- positive CD8 T cells, as well as the OX40- positive CD8 T cells, all of them peaked at the 90 mcg per kg dose. Those were the key drivers, I would say. Of course, together with that, the sort of, the rest of the data that we had. The primary driver was the PD data, and we obviously looked at the safety, and we also had feedback from Key Opinion Leaders, the trial investigators who were treating patients. We got their feedback, and it was pretty much unanimous that 90 mcg per kg would be the ideal dose. Just as a background here, as you know, MDNA11 is a molecule with an IL-2, which is substantially more potent than the Nektar molecule. At 90 mcg per kg, we are already, with respect to the dose, several-fold higher dose with respect to IL-2 equivalent, when you compare it to Nektar's molecule. As you recall, that was about 6 mcg per kg. In the case of MDNA11, we are already at triple that dose with the 90 mcg per kg dose. We feel quite comfortable. There is obviously room to perhaps proceed higher. One thing I will say is that, while we will be conducting our dose expansion at the 90 mcg per kg, as you know, with the FDA's requirement for, you know, Project Optimus, we will continue to evaluate and optimize different dosing schedules and different doses in parallel while the dose expansion is pursuing and get more data through the different, 60 mcg, 90 mcg, and 120 mcg as well. I'll pass it on to Arash, maybe perhaps if you can provide any additional color to this. Thank you very much, Fahar, and thank you, Matt, for your thoughtful question. I mean, I would just reiterate essentially that I think looking at the totality of the dose escalation data, what we're seeing with the 90 mcg per kg dose from an immunological perspective, appears to be optimal, really. I think based on the, the multiple measurements that we presented there. Really, I think at a high level, I think the key message for you and those joining us, is essentially what we were interested in here is not just obviously identifying a dosage which produces robust expansion of key effector cells with respect to the peripheral blood compartment. We were particularly interested in making sure that we attained high degree of quality with respect to the tumor killing capacity of those cells. I think as you've seen with the data accumulated to date, albeit preliminary, we've got multiple orthogonal readouts suggesting really that there is a sweet spot around that 90 mcg per kg dosage. I think that being said, we do have preliminary, from my perspective, evidence of, of clinical activity. We presented the individual with stable disease, the individual with cutaneous malignant melanoma, which was stage four, and the initial SD that was subsequently confirmed, was in fact achieved at a much lower dose, in fact, the 90 mcg per kg. The other patient with the pancreatic ductal adenocarcinoma, again, evidence of clinical activity within the dose range that we're seeking to expand into. I think putting all that together, and then with the security of knowing actually that there will be ongoing evaluation and refinement of both dose and schedule in other tumor types beyond those in the expansion that we've specified, I think gives us a high degree of assurance that this is the right thing to do with respect to the molecules development at this point in time. Understood. Thanks very much for the question. Our next question will come from Charles Zhu with Guggenheim. You may now go ahead. Hi, guys. This is Edward on for Charles. Maybe just some color on the rationale behind selecting the monotherapy dose expansions in melanoma, the non-melanoma skin cancer, and then the MSI-high patients. Also as a follow-up, is that pancreatic. Maybe I missed this, but is that pancreatic cancer patient, do we know if he's MSI-high already or? Just some clarity there, too. Thank you. Sure. Yeah. again, Arash, maybe you can elaborate on that, if you don't mind. Yeah, happy to, thanks very much for the question, Edward. So we obviously gave a lot of thought to the expansion tumor selection. Part of that was even agnostic, even before, obviously, obtaining the clinical data that we have in dose escalation, just on basic scientific grounds and the field's understanding of the immunobiology of those specific tumors that we've specified, there were already very good reasons for selecting those tumors. Obviously, I think metastatic malignant melanoma doesn't really need much in the way of substantiation there. We know with respect to Proleukin, that's an approved indication. We know that there are, in a small proportion of patients, prolonged responses, and we know, obviously, that metastatic melanoma is a very important testing ground, particularly with respect to demonstration of single agent activity. Actually, making this a data-driven decision, obviously, we're coming back to that individual who had had previous immunotherapy, in fact, two lines of immunotherapy, including a doublet with CTLA-4 and anti-PD-1. That individual, really, I think from a clinical benefit perspective, I mean, I let you draw your own conclusions, but this individual really did have stable disease for a very prolonged period of time, despite unequivocal progression on the most recent line of checkpoint inhibition, actually. That would actually argue that, you know, melanoma should be very much one of those expansion tumor types. With respect to the third one, the one that you've listed, the MMR, the dMMR or MSI-H. Perhaps if we just take a step back and just contextualize for the broader set of listeners on the call, why we at Medicenna have a high degree of confidence that this is a very attractive tumor indication to go after. The rationale is really as follows: one is, what is MMR? This MMR pathway, this DNA mismatch repair pathway, is a repair mechanism. Its function is to maintain genomic stability. There are effectively several enzymes, we call these DNA mismatch repair enzymes. They're encoded by four different genes. What these do is basically identify and then repair mismatches within what we call nucleotides during, for example, genetic recombination that may occur as a result of damage that occurs in the context of cancer. The importance of this is that we know that if there are mutations in those, whether those are somatic, and that is known as Lynch syndrome, or whether those are sporadic mutations, we know that those individuals are characterized by a very large number of somatic mutations. Typically, they would harbor in hundreds to thousands of mutations. They would then potentially encode neoantigens, and therefore, those tumors are likely to be immunogenic. We know actually that these tumors tend to be typically very responsive to immunotherapy in the form of checkpoint inhibition. I think from a scientific consideration, that would therefore be very attractive to test MDNA11 in, in the setting of the post PD-1 setting. In other words, in the setting of patients who have unmet medical needs, who progressed on standard of care, and as an oncologist, you're looking at them and, and thinking, "What else do I have to offer my patient?" That's kind of the scientific rationale. Then, as you rightly allude to, Edward, the patient with pancreatic ductal adenocarcinoma was, was clearly a very intriguing result for us, and this patient continues on study, which I think is really very, very, very exciting for us at Medicenna. Yes, this individual has turned out to be MSI-High, and that, therefore, obviously explains why that patient was also given KEYTRUDA. Now, importantly, that patient had progressed on KEYTRUDA. We know that, with respect to even patients who harbor MSI-High or dMMR, a substantial proportion of those patients actually won't respond to checkpoint inhibition. I think putting all those things together, I think those are two very attractive tumor types. The third one, which I think you didn't mention, but is, again, within the expansion set of tumors that we're interested in, are the non-melanoma skin cancers. Again, there is a broad continuity with the other two. What I mean by that is these are amongst the tumor types, solid tumor types, that harbor the highest number of tumor mutations. Put another way, the tumor mutation load, if you like, or burden, it tends to be particularly high in these. Again, we know that they would tend to be immunotherapy responsive. Putting all those together in the post PD-1 setting, we felt on balance, and we did pressure test this extensively, actually, with our Clinical Advisory Board and other external KOLs, that this was a thoughtful step for Medicenna with respect to monotherapy evaluation for MDNA11. Our next question will come from David Martin with Bloom Burton. You may now go ahead. Thank you for taking my questions. I think you've said in the dose expansion that, we should see less heavily pretreated patients. I'm wondering, you know, what changes you'll make to the inclusion/exclusion criteria to achieve this. Do you think this will make patients more responsive to MDNA11? Did you see evidence in the dose escalation that the patients that were more heavily pretreated, were more likely to progress? Yeah, I can. T hanks, David, for the, for the call. Yes, we, we have obviously, from an inclusion/exclusion criteria, refined the patient population, the prognostic factors, et cetera, with respect to the inclusion/exclusion in the phase II portion of the study, which is the dose expansion portion of the study. I'd let Arash perhaps further cover that as he's been closely involved in the study design. Arash? Thanks so much, Fahar. Thanks, David, for the question. I think, again, we a lot of thought, a lot of deep thought to this, and as you rightly highlight, actually, the beauty now is that we can make this data-driven with respect to dose escalation. I think my response to you at a high level would be, absolutely, there are factors that, again, from a preliminary perspective, from the number of patients rated in dose escalation, who seem to be with response with respect to stable disease, stand out we've highlight a little bit earlier, earlier today. You know, they tend to want, for example, factors that you might expect a more genetic. For example, the physiological reserve of the individual, you know, how those. I think, you know, unfortunately, particularly as is typical, this escalation with the initial dose, what you typically enroll there are, are really very, very, to typically succumb very quickly to their illness. Remember, the tumor response, that was fairly, I think that's one aspect, the physical robustness. We've anticipated some inclusive around that. The second aspect is the tumor types. Just as Edward mentioned earlier, the picture of the tumor types is important. Melanoma, you might say, well, look, you've looked at melanoma, what changes here? I think there are a number of very differences that I would happily share with you at this point. Is that they of the number of therapies, and it's the, meaning something that is realistic and would therefore have external validity from a perspective of being extrapolated and being of relevance to, you know, later-stage studies words. The second aspect that's always very important is really tight and careful articulation of that population with respect to their resistant state in participants. Actually, we've got, obviously a lot of thought information from the de-escalation, and we've, we've focused, we've focused the, the expansion specifically on areas of what we think unmet medical need and the rightly defined patient subpopulation with respect to how they progress on prior. Okay, Arash, you are breaking up a lot. I know you tried to cover the key issues, but let me summarize here. David, apologies for the poor quality of sound. Suffice it to say that as Arash pointed out, in the phase I trial, we were really looking at a broad range of tumor types, which is not the case now. We sort of focused on tumor types that are potentially immunogenic and therefore most likely to respond to MDNA11. Second of all, is that the patients would have all had received prior checkpoint inhibition therapy. That is important because those are the patients that tend to have a sort of a much better immune reserve and therefore more likely to benefit from MDNA11. That's, those are the two key features here, and of course, the number of lines of therapy, et cetera, may be important. I think more importantly, what we need to make sure is that the patient's immune reserve is healthy, and that's something that we did not do, necessarily in the sort of the phase I portion of the trial. Hopefully that sort of surprises what, Arash was trying to, communicate. Okay, thanks for clearing that up. Second quick question. Two patients are still on trial, it appears in cohort six, and one of them it looks like you haven't had a scan yet. When's the first scan gonna happen for that patient, and when will the second scan be for the patient that has stable disease and continues in that cohort? The two patients you're referring to are, one is a melanoma patient, and one is the RCC patient. The melanoma patient, expect that was stable disease in the first scan. The second scan is probably occurring sometime in early to mid-September. These are sort of 12 weeks apart. The RCC patient should be in the process of getting a scan imminently. We should be aware of that patient's response rather quickly. Okay, thanks. That's it for me. Our next question will come from Catherine Novack with Jones Research. You may now go ahead. Hi, good morning. Congrats on the data, and thanks for taking my question. I wanted to ask about some of the safety data that you presented. Can you tell us, you know, at which dose levels you saw some of these grade three events, especially the elevated liver enzyme? Were these resolved, or did they lead to discontinuation? Right. Thank you, Catherine, for your call. Appreciate that. Nevertheless, I think if you look at the slide, which is slide nine, the majority of events, as you know, were grade one and two. They were mostly of short duration. The elevation of liver enzymes, I think that's the one that you specifically mentioned. Those again, we found and this has been something which is very typical with IL-2 in particular. These effects were short-lasting. In most cases, the enzyme levels decreased and came back to baseline within a few days. These were not perpetuating for a longer period of time. It didn't matter really, whether, you know, in terms of the grade per se or the extent or duration, it was pretty much, you know, certainly at the mid and higher doses, more readily apparent. Nevertheless, in all cases, the, the levels came down back to baseline very, very quickly. I don't know if Arash is there and able to add. Thanks, Fahar. No, exactly. Catherine, I think to the best of my recollection, they were scattered in terms of their. Your question, I think, is around the transaminase elevation, the grade three. My recollection is that they were scattered across the sort of intermediate to higher dose levels. In other words, across the 60, 90, and 120. You know, there wasn't, therefore, to date, clear evidence of a dose toxicity relationship with respect to that metric. I think as Fahar has highlighted, actually, these were without any obvious clinical sequelae. In other words, these were laboratory observations and did not require any specific interventional management and spontaneously resolved. I think perhaps it's important just in terms of broader context, just to recollect, actually, that is a very well-recognized consequence of IL-2 therapy, actually. In other words, the majority of patients will have some form of transient transaminase elevation associated with the administration of high-dose IL-2. Okay, got it. That's very helpful. Then I just have one more question. You know, obviously, it's very early and understanding the sample size is small, but it seems that we see outliers in each cohort in terms of T-cell lymphocyte expansion. Do you have any details on whether these were in the same patients who achieved, stable disease, a partial response? Are you seeing any association in that regard? Yeah, Cat, that's again, a good question. As you alluded to, obviously the number of patients is quite small for us to provide any kind of correlation whatsoever. The trends are there in terms of dose dependency. We do see 90 mcg showing some unique ability to expand certain highly potent variants of CD8 T cells. As we collect more data over time, I think we'll be able to better see if there's some kind of a correlation. It'd be always good to have some kind of a relationship data that would allow us in the future to select patients. Certainly, nothing that's appearing or is appearing to be obvious with respect to response versus PD markers. The only thing I could say is that what we do have access to is Proleukin's data that's been published multiple times. I think one of the things that's apparent is that when you get to lymphocyte counts that have increased two or threefold relative to baseline, those patients tend to respond to therapy. We see that with 90 mcg per kg and 120 mcg per kg, which is we cross that threshold. The other thing also with IL-2, again, the high-dose Proleukin, has been that, you know, patients that don't respond to high-dose IL-2 are patients that express or have high levels of ICOS positive Tregs. You know, you'll see from our data, particularly at the sort of the 90 mcg per kg dose, or in fact, at all the doses of 60 mcg per kg to 120 mcg per kg, we don't see much of an increase in the population of ICOS positive Tregs. Again, an encouraging sign that that could, you know, provide us some context in the sense that clearly we are not boosting that highly immunosuppressive population of ICOS Tregs. And the unique features that we are substantially increasing the population of CD25, ICOS- positive, and OX40 CD8 T cells across the board, but it's been nothing that we've been able to correlate in terms of response, et cetera. Too early to say. Got it. That's, that's very helpful. Thanks again for taking my questions. Again, if you have a question, please press star then one. Our next question will come from Swayampakula with, Swayampakula Ramakanth with H.C. Wainwright. You may now go ahead. Thank you. Good morning, Fahar and Dr. Yavari. I appreciate it. Appreciate the call and the details. I understand your rationale behind the 90-mcg dose based on what you're seeing on the CD8 T cells and the Tregs. However, when you look closely at that 90-mcg cohort, between the two melanoma patients that were on the study, one of them progressed and passed away, whereas the other patient has achieved stable disease. Is there any difference between these two patients in terms of their treatment history and, I'm just trying to understand. When you look at the totality of the, of the patients who are on this study, especially if you look at the swim plot, more, more, more melanoma patients seem to have progressed and, and passed away, whereas with other tumors, they seem to be progressing, but at least as of now, they're all alive. I'm just trying to understand how this is this can impact OS data when, when we get, get there. Right. Thanks, RK. Thanks for the call. Appreciate your question. I'll try and answer as best as I can, but then pass it on to Arash as well. Suffice it to say that first and foremost, the patients in cohort five, as you can imagine, they somehow ended up being quite elderly patients. These were all patients that were either 73, 74, or 75 years old. Obviously, quite old patients. You know, relative to our median age, which is in the 60s, these patients were a lot more older. The other thing is that, with respect to the patient that's demonstrating some stable disease, this particular patient did respond to initial treatment with nivolumab as a first-line therapy and had, in fact, a complete response before the patient had progression. That may be the case, whereas the patient in, so that, that's progressed, did not respond to ipi/nivo combo. It could be. There might be some role here with respect to the treatment regimen and, and the sort of the, the tumor itself not responding to a checkpoint inhibitor in the, in one case, where it's responding to the checkpoint in, in the first case. I'll sort of pass it on to Arash, and maybe you can elaborate a bit more on that. Yeah, thanks very much, Fahar. I mean, I would just obviously add a, a note of caution here that we are dissecting essentially individual patient profiles at a very early stage in the program. I think it comes back to David's thoughtful question around: What are you doing differently with respect to the expansion phase? I think Fahar's already alluded to some of those features. Our assessment, I think, at this point in time, is that there are significant differences between those two individuals that you kindly highlighted. Where there appears to be a difference, you know, one having stable disease, one unfortunately succumbing to disease progression really very rapidly. The significant differences, for example, encompass primarily previous treatment history and how heavily pretreated they were. In fact, the patient from recollection in cohort five, who did progress, was amongst the most heavily pretreated from an IO as well as in fact, targeted perspective. The individual had, had non-immune checkpoint blockade therapy, so BRAF/MEK inhibition as well. That individual actually, I think in the context of any dose escalation study, having had multiple different prior lines of either remarkable failures, would have been unfortunately marked out as a very, very high bar for any for any molecule as a as a single agent. Thank you. One additional question from me. On the dose expansion phase for the combination study with pembrolizumab, right now you only defined one indication, and you kept it open for the additional indications. Will that decision be made based on what you see in the monotherapy part of the dose expansion phase? Is it that you're waiting for additional data, additional follow-up data from the dose escalation piece, to fill in to decide on the other additional patient groups? Yeah, again, not necessarily with respect to waiting for additional data or waiting for any data from the dose expansion. That's not going to be the sort of the determining factor going forward. Certainly, as Arash alluded to very early on, when we selected the patient population for the dose expansion monotherapy setting, we did have extensive discussions with KOLs, and investigators who have previously treated patients with IL-2, patients that have received a combination of these compounds with checkpoint inhibitors as well. We are really looking at the feedback and input we compiled together, which is currently underway. Of course, we'll be also having discussions with the clinical collaborator, Merck, with respect to where we think there might be opportunities with MDNA11 in a combination setting. No, we will not be waiting for the dose expansion data to mature. Arash, do you want to add anything else? I think you've covered it well, Fahar. Okay, great. Thank you. Thanks for taking my questions. You're welcome. Thanks. This concludes our question and answer session. I would like to turn the conference back over to Fahar for any closing remarks. Well, thanks, operator. It's been a pleasure sharing our updates with all listening today. I thank you for your participation. Our recent progress has strengthened the outlook of our pipeline. We really look forward to providing periodic updates as our MDNA11 program continues to progress. Thank you all for joining. Have a great day. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.